(Journal of Leukocyte Biology. 2001;69:691-697.)
© 2001
by Society for Leukocyte Biology
Participation of mammalian defensins and cathelicidins in anti-microbial immunity: receptors and activities of human defensins and cathelicidin (LL-37)
De Yang,
Oleg Chertov and
Joost J. Oppenheim
Laboratory of Molecular Immunoregulation, Division of Basic Sciences, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland
Correspondence: Dr. Joost J. Oppenheim, LMI, DBS, NCI-Frederick, Building 560, Room 21-89, Frederick, MD 21702-1201. E-mail: oppenhei{at}mail.ncifcrf.gov
 |
ABSTRACT
|
|---|
Defensins and cathelicidins are the two major families of mammalian
anti-microbial proteins. They contribute to host, innate,
anti-microbial defense by disrupting the integrity of the bacterial
cell membrane. However, several members of the mammalian anti-microbial
proteins including defensins and cathelicidins have been shown recently
to have chemotactic effects on host cells. Human neutrophil
-defensins are chemotactic for resting, naïve CD45RA/CD4 T
cells, CD8 T cells, and immature dendritic cells. Human ß-defensins
are also chemotactic for immature dendritic cells but induce the
migration of memory CD45RO/CD4 T cells. In contrast, cathelicidin/LL-37
is chemotactic for neutrophils, monocytes, and T cells but not for
dendritic cells. Thus, these anti-microbial peptides have distinct,
host-target cell spectra. The chemotactic activities of human
ß-defensins and cathelicidin/LL-37 are mediated by human CC chemokine
receptor 6 and formyl peptide receptor-like 1, respectively. The
capacities of defensins and cathelicidins to mobilize various types of
phagocytic leukocytes, immature dendritic cells, and lymphocytes,
together with their other effects such as stimulating IL-8 production
and mast cell degranulation, provide evidence for their participation
in alerting, mobilizing, and amplifying innate and adaptive
anti-microbial immunity of the host.
Key Words: chemotaxis • CCR6 • FPRL1 • phagocytic leukocytes • dendritic cells • keratinocytes • macrophages
|
INTRODUCTION
|
|---|
Animals are under constant bombardment by microorganisms, yet
individuals rarely manifest infection. This is primarily a result of
the barrier function of intact epithelia lining the respiratory,
gastrointestinal, and urogenital tracts and skin, which prevent the
intrusion of microorganisms mechanically and by the constitutive
production of anti-microbial chemicals and proteins [1
,
2
]. Since the identification of the first anti-bacterial
protein family of "thionins" during the early
1970s[3
], over 400 anti-microbial proteins have
thus far been identified in plants, insects, and animals
[1
, 4
5
6
7
8
]. The two major families of
mammalian anti-microbial proteins that have been well-characterized are
defensins and cathelicidins [7
8
9
10
]. Defensins and
cathelicidins have the capacity to kill and/or inactivate bacteria,
fungi, and enveloped viruses in vitro
[7
8
9
10
]. They have also been demonstrated to contribute
to host defense in vivo [11
12
13
]. Thus, it
has become clear that defensins and cathelicidins contribute to
innate, anti-microbial, host defenses.
However, mammalian species manifest two additional types of
anti-microbial defense mechanisms, namely innate and adaptive immunity
[2
, 14
]. Evidence is emerging suggesting
that defensins and cathelicidins may also participate in galvanizing
innate and adaptive anti-microbial immunity [15
,
16
]. This study will summarize the evidence that
defensins, cathelicidins, and perhaps other mammalian anti-microbial
proteins as well, have evolved the capacity to participate in host
innate and adaptive immune responses and to use host receptors to
mobilize and activate various types of leukocytes.
|
A SIMPLE OVERVIEW OF MAMMALIAN DEFENSINS AND CATHELICIDINS
|
|---|
Mammalian defensins consist of a family of cationic proteins that
contain six highly conserved cysteine residues that form three pairs of
intrachain-disulfide bonds. Based on the patterns of their
intrachain-disulfide bridges, mammalian defensins are classified into
three subfamilies, namely -, ß-, and 
-defensins
[7
, 8
, 17
]. Currently, the
-defensin subfamily has only one member that is cyclic with its six
cysteine residues linking C1 to C6, C2 to C5, and C3 to C4
[17
]. The three disulfide bonds of -defensins are
paired C1 to C6, C2 to C4, and C3 to C5 [7
,
9
, 18
], and those of ß-defensins are C1 to
C5, C2 to C4, and C3 to C6 [7
, 19
]. More
than 50 defensin family members have been identified in mammalian
species. The number of defensins varies from one species to another. In
humans, six -defensins and three ß-defensins have been
identified so far [7
8
9
, 20
21
22
23
24
].
Cathelicidins consist of a family of anti-microbial proteins with a
putative N-terminal signal peptide, a highly conserved cathelin
(cathepsin L inhibitor)-like domain in the middle, and a
less-conserved, C-terminal, anti-microbial domain [8
,
10
]. About 20 cathelicidin members have been identified
in mammals, however, only one cathelicidin has been identified in
humans thus far [10
, 25
26
27
]. Cleavage of
human cathelicidin (hCAP18) liberates its C-terminal, anti-microbial
domain, a peptide called LL-37, because it begins with two leucine
residues and is 37 amino-acid residues in length. Thus, human
cathelicidin is often referred to as LL-37 [10
,
28
].
The classifications, origins, and effects on host cells of human
-defensins, ß-defensins, and cathelicidin/LL-37 are outlined in
Table 1 . The expression of defensins and cathelicidins in tissues varies
markedly among mammalian species. Human -defensins 1, 2, 3, and 4
were isolated from neutrophils initially [20
,
21
], so they are termed human neutrophil peptides (HNP)1,
2, 3, and 4 conventionally [7
, 8
]. HNP1, 2,
3, and 4 are stored in the granules of neutrophils and
monocytes/macrophages and can be released extracellularly
[29
, 41
, 42
]. Human
-defensins 5 and 6 (HD5 and 6) are products of intestinal Paneth
cells primarily [9
, 22
, 43
],
although defensin 5 is also detected in reproductive tissues
[44
]. Human ß-defensin (HBD)1 is expressed in
epithelial cells and skin keratinocytes constitutively
[23
, 45
46
47
48
49
50
51
52
]. In contrast, the expression
of HBD2 and 3 by keratinocytes and epithelial cells in various tissues
is induced predominantly by contact with bacteria or microbial products
such as endotoxin or proinflammatory cytokines such as tumor necrosis
factor (TNF) and interleukin (IL)-1 [24
, 46
,
48
, 51
, 53
54
55
].
Cathelicidin/LL-37 is not only stored in neutrophil granules
[26
27
28
] but is also expressed by epithelial cells
constitutively [56
] and keratinocytes in response to
inflammatory stimuli [57
, 58
].
|
THE CHEMOTACTIC ACTIVITIES OF HUMAN DEFENSINS AND CATHELICIDIN
|
|---|
Initially, defensins were discovered as the T cell
chemoattractants released by IL-8-induced neutrophil degranulation.
Sequential chromatography of neutrophil-derived T cell chemoattracting
activities produced in response to IL-8 led to the identification of
HNP1 and HNP2 as the chemotactic moieties for human peripheral blood T
lymphocytes [29
, 42
]. Investigation of
subsets of human T cells demonstrated that HNP is chemotactic for CD4
and CD8 T cells [16
]. Among CD4 T cells, only CD45RA
naïve but not CD45RO memory subset can be chemoattracted by HNP
[16
]. The effect of HNP on human T cells motivated us to
investigate whether HNP could exhibit in vivo
immunomodulatory activities. HNP, when administered in vivo
together with antigens, strikingly enhanced systemic antigen-specific
immune responses in mice, demonstrating that HNP has potent
immunoadjuvant activity [37
, 38
]. This
adjuvant activity of HNP led us to test their effect on dendritic cells
(DC), the professional antigen-presenting cells (APC)
[59
60
61
]. We found that HNP is chemotactic for immature
DC (iDC) generated from purified peripheral blood monocytes or cord
blood CD34 hematopoietic progenitor cells [16
]. The
chemotactic activity of HNP for iDC is highly selective because neither
monocytes nor CD34 cells could be chemoattracted [16
].
Furthermore, when iDC were induced to mature, the resulting mature DC
(mDC) can no longer migrate in response to HNP [16
].
Human ß-defensin is also chemotactic for various types of leukocytes.
HBD2 and to a lesser extent HBD1 induce the migration of human iDC and
CD45RO memory T cells [15
]. Again the chemotactic
activity of HBD shows selectivity, because mDC, CD45RO naïve T
cells, neutrophils, and monocytes could not be chemoattracted by HBD.
Similar to HBD1 and 2, the recently identified HBD3 is also chemotactic
for iDC, but unlike HBD1 and 2, HBD3 is also chemotactic for peripheral
blood monocytes (unpublished results).
Recently, we investigated the human cathelicidin/LL-37 and found that
LL-37 is chemotactic for human peripheral blood neutrophils, monocytes,
and T lymphocytes [39
]. The chemotactic effect of LL-37
on human neutrophils and T cells has also been documented by Agerberth
et al. [40
]. However, in contrast to
defensin, LL-37 is not chemotactic for iDC or mDC [39
].
Along similar lines, PR-39, one member of the porcine cathelicidin
family, is shown to be chemotactic for porcine neutrophils
[62
]. Several other anti-microbial proteins in addition
to defensins and cathelicidins are also chemotactic for various types
of leukocytes. Azurocidin/hCAP37, an anti-microbial protein produced by
human neutrophils, is chemotactic for human T cells
[29
], monocytes [63
, 64
],
and neutrophils [64
]. Cathepsin G, an anti-microbial
protein of the serine proteinase family stored in the granules of
neutrophils, monocytes, and mast cells, is chemotactic for human
neutrophils and monocytes [64
]. Chymase, another member
of the serine proteinase family that is produced primarily by mast
cells and potentially has anti-microbial activity, is a potent
chemoattractant for human neutrophils and monocytes
[65
]. Eosinophil-derived neurotoxin, a human eosinophil,
granule-derived antiviral protein belonging to the ribonuclease family,
is selectively chemotactic for iDC and mDC (unpublished results).
Finally, we observed recently that histatin 5, a member of the salivary
gland-derived anti-microbial histatins, can induce the migration of
human monocytes (unpublished results). However, not every
anti-microbial protein is chemotactic; for example, lysozyme is not
chemotactic for human leukocytes (unpublished results). The chemotactic
activities of various human anti-microbial proteins are summarized in
Table 2
.
|
IDENTIFICATION OF CHEMOTACTIC RECEPTORS FOR HBD AND LL-37
|
|---|
The chemotactic activities of HNP, HBD, and LL-37 share a number
of characteristics. First, they induce chemotaxis of target cells at
considerably lower doses than those required for their anti-microbial
effects. To exert optimal anti-microbial effects in vitro,
HNP, HBD, and LL-37 generally require concentrations higher than 10
µg/ml. However, HNP induce optimal target-cell migration at
concentrations ranging from 10 to 100 ng/ml [16
,
29
], and HBD attracts target cells at an optimal
concentration of 100–1000 ng/ml [15
]. Concentrations of
300–3000 ng/ml LL-37 are needed to induce chemotaxis of target cells
[39
]. Secondly, the chemotactic activities of defensins
and LL-37 exhibit a bell-shaped, dose-response curve [15
,
16
, 29
, 39
] typical of
chemotactic factors [66
, 67
]. Thirdly,
their chemotactic activities are not affected [15
,
16
, 29
, 39
] by serum at
concentrations that, as demonstrated, inhibit their anti-microbial
effects [7
, 68
]. Lastly, their chemotactic
activities are highly selective on target cells, suggesting a
receptor-mediated mechanism.
The possibility that defensins and LL-37 use G protein-coupled,
seven-transmembrane-domain receptor(s) to attract their target cells
was tested because defensin- and LL-37-induced chemotaxis could be
inhibited by pertussis toxin [15
, 16
,
39
], a reagent capable of inhibiting Gi
protein-coupled, seven-transmembrane-domain receptors
[66
, 67
, 69
]. The fact that
HNP and HBD induce the migration of iDC but not mDC [15
,
16
] motivated us to focus on chemotactic receptors
expressed selectively iDC (but not by mDC), such as CXCR1, CXCR2, CCR1,
CCR2, CCR4, CCR5, CCR6, and formyl peptide receptor (FPR)
[70
71
72
73
]. Examination of cells transfected to express
one of the above candidate receptors demonstrated that only human
CCR6-transfectant cells were capable of migrating in response to HBD1
and HBD2, implicating CCR6 as a chemotactic receptor for HBD
[15
]. Additional key evidence in support of this
conclusion includes: 1) HBD2-induced chemotaxis of CCR6-transfectant
cells can be cross-desensitized by LARC, the previously identified
ligand for CCR6 [69
, 72
], and vice versa;
2) HBD2 can inhibit the binding of iodinated LARC to CCR6-transfectant
cells competitively; and 3) HBD2-induced migration of human iDC can be
inhibited dose-dependently by anti-human CCR6 antibody. Thus, CCR6 is a
functional receptor that HBD uses to mediate its chemotactic effect
[15
]. HNP also seems to use a chemokine receptor to
mediate its chemotactic effect, but its identity is still unknown
[16
].
LL-37 induces not only chemotaxis but also
Ca+2+ flux in monocytes [39
].
Therefore, we investigated the capacity of dozens of chemotactic
factors, including all of the chemokines and chemoattractants, to
determine which one was able to cross-desensitize LL-37-induced
Ca2+ flux in monocytes. This identified an
agonistic ligand specific for FPR-like 1 receptor (FPRL1), indicating
that LL-37 uses FPRL1 as a receptor to mediate its action on monocytes
[39
]. Human peripheral blood neutrophils and T
lymphocytes, cells known to express functional FPRL1 [67
,
74
], can also migrate chemotactically in response to
LL-37, providing additional evidence for this conclusion
[39
]. Furthermore, LL-37 induces the migration of cells
transfected to express FPRL1 but not cells transfected to express FPR,
a chemotactic receptor showing the highest homology with FPRL1. These
data enabled us to conclude that FPRL1 is a functional receptor for
LL-37 [39
].
|
OTHER ACTIVITIES OF HUMAN DEFENSINS AND CATHELICIDIN/LL-37
|
|---|
Anti-microbial proteins have been shown to have a variety of
biological effects on the host in addition to leukocyte chemotaxis
(Table 1) . HNP has been shown to cause mast cell degranulation
[75
], stimulate IL-8 production by human bronchial and
lung epithelial cells [30
, 31
], modulate
complement activation [32
33
34
], suppress glucocorticoid
production [35
, 36
, 76
,
77
], and enhance the proliferation of T cells and their
production of cytokines [37
]. The effects of neutrophil
-defensins on complement activation are mediated by binding to
complement C1 [32
33
34
], and the capacity of neutrophil
-defensins to suppress glucocorticoid production is achieved by
blocking the binding of adrenocorticotropic hormone to its receptor
[35
, 77
]. However, the capacities of
defensins and cathelicidins to stimulate cytokine production and cause
mast-cell degranulation may also be mediated by receptor-based
mechanisms.
|
INCORPORATION OF DEFENSINS AND CATHELICIDINS IN ANTI-MICROBIAL
IMMUNITY
|
|---|
Mammalian host defenses comprise innate and adaptive immune
components [2
, 14
, 78
]. Innate
immunity represents the first line of host defense and is triggered
rapidly following the detection by pattern recognition receptors of
pathogen-associated molecular patterns (e.g., lipopolysaccharide,
teichoic acid, peptidoglycan, mannan, and double-strand RNA) that are
unique to microorganisms [2
, 78
]. The
effector branch of innate immunity consists of two major aspects. One
is the release and, at times, activation of a variety of extracellular
humoral mediators such as complement, cytokines, and anti-microbial
proteins including defensin and cathelicidin. The other is the
recruitment and activation of phagocytic granulocytes,
monocytes/macrophages, and in some cases natural killer (NK) cells to
sites of microbial invasion to combat the invading pathogens. Adaptive
immunity is induced when T lymphocytes are activated in response to
antigens presented by APC in conjunction with major histocompatibility
complex (MHC) class I and class II molecules and concomitant
APC-derived costimulatory signals [14
, 61
,
78
, 79
]. The T helper cells, in turn,
promote antigenic activation of B cells, which results in the
production of antigen-specific antibodies that neutralize
pathogen-derived toxins, block the infectivity of invading pathogens,
and promote their opsonization and elimination by phagocytes. T cell
activation generates CD4 and CD8 effector T cells that produce
cytokines capable of activating phagocytes to eliminate pathogens more
efficiently and also kill cells infected by intracellular pathogens
directly. Thus, adaptive immunity, in addition to resulting in clonal
expansion of T and B cells, also further activates and promotes innate
host defenses.
Some of the defensins (e.g., HBD1) and cathelicidins are produced
constitutively by keratinocytes and other epithelial cells and
contribute to the barrier functions that provide a first line of
defenses against microbial invasion of the host. Pathogens that succeed
in penetrating the barrier of epithelia and skin stimulate an increase
in the production and release of -defensins, ß-defensins (in
particular, ß-defensins 2 and 3), and cathelicidins by epithelial
cells, skin keratinocytes, and tissue macrophages. Thus, defensins and
cathelicidins generated form local chemotactic gradients as shown in
Figure 1
and have a number of other effects. 1) They kill invading
pathogens directly. 2) HNP is capable of stimulating IL-8 production by
human airway epithelial cells by augmenting IL-8 gene transcription
[30
, 31
]. Because IL-8 is a potent
neutrophil recruiter [66
, 69
], it is
conceivable that defensins and cathelicidins promote neutrophils to
migrate to sites of pathogen invasion based on their chemotactic
activities [29
, 39
] or indirectly through
the induction of IL-8 [30
, 31
]. This
results in a positive-feedback loop because recruited neutrophils
release additional defensins and cathelicidins to amplify innate immune
responses against invading pathogens. 3) They activate phagocytes to
eliminate pathogens more efficiently [80
]. 4) They
degranulate mast cells leading to the release of mast-cell granule
products including histamine [75
, 81
].
Several guinea pig, human, rabbit -defensins, HBD2, and LL-37 are
able to degranulate rat peritoneal mast cells resulting in the release
of mast-cell granule products including histamine [75
,
81
]. Because mast cells modulate neutrophil influx and
bacterial clearance, and histamine is known to be able to increase the
permeability of small blood vessels [82
,
83
], defensin- and cathelicidin-induced release of
mast-cell granule products including histamine would help in the
recruitment of more neutrophils to the inflammatory sites. 5) Finally,
these mediators of innate host defense also provide the initial signals
that mobilize DC and T cells and thus alert the adaptive immune
responses.
View larger version (71K):
[in this window]
[in a new window]
|
Figure 1. Schematic illustration of the participation of human defensins and
cathelicidin/LL-37 in innate host defense and adaptive immunity against
microbial invasion. Upon microbial invasion, epithelial
cells/keratinocytes and tissue macrophages (M ) are induced to
produce ß-defensins (esp. HBD2 and 3) and cathelicidin/LL-37. Beside
their several effects on innate host defense, the defensins and
cathelicidin form gradients, which, in concert with other chemotactic
mediators (e.g., chemokines), result in the extravasation of various
types of leukocytes to the site of infection. Recruited neutrophils
(PMN) release -defensins and more cathelicidin that amplify
leukocyte recruitment further. Recruitment of PMN and monocytes (Mo)
enhances innate host defense, and recruited iDC and T cells promote the
induction phase and effector phase, respectively, of adaptive
anti-microbial immunity. Human ß-defensins use CC chemokine receptor
6 (CCR6) as a receptor, whereas the receptor for LL-37 is FPRL1. As
denoted by a question mark, the receptor for HNP -defensins has not
been identified yet.
|
|
DC are the most potent APC and the only APC that have the capacity to
activate naïve CD4 T cells [59
60
61
]. However, DC
have to migrate to sites of pathogen invasion for antigen uptake and
processing and must mature to be able to migrate to T cell areas of
secondary lymphoid organs for antigen presentation to naïve CD4
T cells [15
, 61
, 70
71
72
73
].
Defensins contribute to the induction of adaptive, anti-microbial
immune response by recruiting more iDC to the sites of pathogen
invasion chemotactically [15
, 16
]. In
addition, defensins and cathelicidins can also promote DC accumulation
at the inflammatory sites by degranulating mast cells
[75
, 81
]. Mast-cell degranulation releases
platelet-activating factor (PAF), a potent chemoattractant for DC
[84
]. Furthermore, activated T cells also migrate to the
sites of pathogen invasion to exert some of their effector functions.
Defensins and cathelicidins facilitate T cell recruitment because they
are both chemotactic for T cells [15
, 16
,
29
, 39
]. Thus, anti-microbial proteins of
innate host defense, in particular, defensins, also have a bridging
function of activating adaptive, anti-microbial immune responses.
The capacity of defensins to induce iDC migration would suggest the
possibility that defensin can act as in vivo adjuvants.
Indeed, when administered together with antigens, HNP can enhance
antigen-specific humoral and cellular immune responses
[37
, 38
], providing further support for the
concept that anti-microbial proteins also participate in host adaptive
immunity. Defensin and cathelicidin may also influence systemic
anti-microbial immunity by inhibiting immunosuppressive glucocoticoids
and neutralizing endotoxins. Nanomolar concentrations of -defensins
are demonstrated to inhibit the production of immunosuppressive
glucocorticoids [35
, 36
, 76
,
77
]. In the course of systemic infections, serum levels
of -defensin can reach up to 100 µg/ml [85
,
86
], which is more than sufficient for inhibiting
glucocorticoids. Cathelicidin has been shown to be capable of binding
and neutralizing lipopolysaccharide [25
,
87
], so it can ameliorate endotoxin shock
[87
]. It is reasonable to predict that defensins and
cathelicidins cooperate in vivo with many other mediators of
host defense, such as cytokines, chemokines, complement, acute-response
proteins, other animicrobial proteins, and cellular components in
generating an orchestrated defense against invading pathogens
[2
, 69
, 78
, 88
].
|
SUMMARY AND PERSPECTIVE
|
|---|
Although it is reasonably well-established that mammalian
anti-microbial proteins including defensins and cathelicidins play an
essential role in host innate, anti-microbial immunity, their
participation in host adaptive, anti-microbial immunity has just begun
to unfold. We have reviewed the chemotactic activities and receptors
used by human defensins and cathelicidin/LL-37 as well as their
potential participation in innate and adaptive (in particular,
anti-microbial) immunity. However, many questions remain to be answered
and experimentally addressed. The receptor(s) HNP uses to mediate its
chemotactic activity remains to identified. Are Paneth cell-derived
defensins (HD5 and 6 in humans) also chemotactic? Do defensins and
cathelicidins of other species also have the capacity to mobilize
various types of host leukocytes? How are the chemotactic activities of
anti-microbial proteins other than defensins and cathelicidins
mediated? How many anti-microbial peptides remain to be identified? It
is our hope that this review will stimulate more interest and attention
to this particular area.
|
ACKNOWLEDGEMENTS
|
|---|
The content of this publication does not necessarily reflect the
views or policies of the Department of Health and Human Services nor
does mention of trade names, commercial products, or organizations
imply endorsement by the U.S. Government. The publisher or recipient
acknowledges the right of the U.S. Government to retain a nonexclusive,
royalty-free license in and to any copyright covering the article.
Received November 5, 2000;
revised December 22, 2000;
accepted December 28, 2000.
|
REFERENCES
|
|---|
-
Boman, H. G. (1995) Peptide antibiotics and their role in innate immunity Annu. Rev. Immunol. 13,61-92[Medline]
-
Hoffmann, J. A., Kafatos, F. C., Janeway, C. A., Jr, Ezekowitz, R. A. B. (1999) Phylogenetic perspectives in innate immunity Science 284,1313-1318[Abstract/Free Full Text]
-
Fernandez-de-Caleya, R., Gonzales-Pasqual, B., Garcia-Olmedo, F., Carbonero, P. (1972) Susceptibility of phytopathogenic bacteria to wheat purothionins in vitro Appl. Microbiol. 23,998-1000[Medline]
-
Boman, H. G. (1998) Gene-encoded peptide antibiotics and the concept of innate immunity: an update review Scand. J. Immunol. 48,15-25[Medline]
-
Broekaert, W. F., Terras, F. R. G., Cammue, B. P. A., Osborn, R. W. (1995) Plant defensins: novel anti-microbial peptides as components of host defense system Plant Physiol 108,1353-1358[Medline]
-
Steiner, H., Hultmark, D., Engstrom, A., Bennich, H., Boman, H. G. (1981) Sequence and specificity of two antibacterial proteins involved in insect immunity Nature 292,246-248[Medline]
-
Ganz, T., Lehrer, R. I. (1994) Defensins Curr. Opin. Immunol. 4,584-589
-
Lehrer, R. I., Ganz, T. (1999) Anti-microbial peptides in mammalian and insect host defense Curr. Opin. Immunol. 11,23-27[Medline]
-
Ouellette, A. J., Selsted, M. E. (1996) Paneth cell defensins: endogenous peptide components of intestinal host defense FASEB J 10,1280-1289[Abstract]
-
Zanetti, M., Gennaro, R., Romeo, D. (1995) Cathelicidins: a novel protein family with a common proregion and a variable C-terminal anti-microbial domain FEBS Lett 374,1-5[Medline]
-
Wilson, C. L., Ouellette, A. J., Satchell, D. P., Ayabe, T., Lopez-Boado, Y. S., Stratman, J. L., Hultgren, S. J., Matrisian, L. M., Parks, W. C. (1999) Regulation of intestinal -defensin activation by the metalloproteinase matrilysin in innate host defense Science 286,113-117[Abstract/Free Full Text]
-
Bals, R., Weiner, D. J., Meegalla, R. L., Wilson, J. M. (1999) Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model J. Clin. Invest. 103,1113-1117[Medline]
-
Bals, R., Weiner, D. J., Moscioni, A. D., Meegalla, R. L., Wilson, J. M. (1999) Augmentation of innate host defense by expression of a cathelicidin anti-microbial peptide Infect. Immun. 67,6084-6089[Abstract/Free Full Text]
-
Thompson, C. B. (1995) New insights into V(D)J recombination and its role in the evolution of the immune system Immunity 3,531-539[Medline]
-
Yang, D., Chertov, O., Bykovskaia, S. N., Chen, Q., Buffo, M. J., Shogan, J., Anderson, M., Schroder, J. M., Wang, J. M., Howard, O. M. Z., Oppenheim, J. J. (1999) ß-Defensins: linking innate and adaptive immunity through dendritic and T cell CCR6 Science 286,525-528[Abstract/Free Full Text]
-
Yang, D., Chen, Q., Chertov, O., Oppenheim, J. J. (2000) Human neutrophil defensins selectively chemoattract naïve T and immature dendritic cells J. Leukoc. Biol. 68,9-14[Abstract/Free Full Text]
-
Tang, Y-Q., Yuan, J., Osapay, G., Osapay, K., Tran, D., Miller, C. J., Ouellette, A. J., Selsted, M. E. (1999) A cyclic anti-microbial peptide produced in primate leukocytes by the ligation of two truncated -defensins Science 286,498-502[Abstract/Free Full Text]
-
Zhang, X-L., Selsted, M. E., Pardi, A. (1992) NMR studies of defensin anti-microbial peptides: 1. Resonance assignment and secondary structure determination of rabbit NP-2 and human HNP-1 Biochemistry 31,11348-11356[Medline]
-
Tang, Y-Q., Selsted, M. E. (1993) Characterization of the disulfide motif in BNBD-12, an anti-microbial ß-defensin peptide from bovine neutrophils J. Biol. Chem. 268,6649-6653[Abstract/Free Full Text]
-
Ganz, T., Selsted, M. E., Szklarek, D., Harwig, S. S. L., Daher, K., Bainton, D. F., Lehrer, R. I. (1985) Defensins: natural peptide antibiotics of human neutrophils J. Clin. Invest. 76,1427-1435
-
Wilde, C. G., Griffith, J. E., Marra, M. N., Snable, J. L., Scott, R. W. (1989) Purification and characterization of human neutrophil peptide 4, a novel member of the defensin family J. Biol. Chem. 264,11200-11203[Abstract/Free Full Text]
-
Mallow, E. B., Harris, A., Salzman, N., Russell, J. P., DeBerardinis, R. J., Ruchelli, E., Bevins, C. L. (1996) Human enteric defensins: gene structure and developmental expression J. Biol. Chem. 271,4038-4045[Abstract/Free Full Text]
-
Bensch, K. W., Raida, M., Magert, H-J., Schulz-Knappe, P., Forssmann, W-G. (1995) hBD-1: a novel ß-defensin from human plasma FEBS Lett 368,331-335[Medline]
-
Harder, J., Bartels, J., Christophers, E., Schroder, J. M. (1997) A peptide antibiotic from human skin Nature 387,861[Medline]
-
Larrick, J. W., Hirata, M., Balint, R. F., Lee, J., Zhong, J., Wright, S. C. (1995) Human CAP18: a novel anti-microbial lipopolysaccharide-binding protein Infect. Immun. 63,1291-1297[Abstract]
-
Cowland, J. B., Johnsen, A. H., Borregaad, N. (1995) hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules FEBS Lett 368,173-176[Medline]
-
Agerberth, B., Gunne, H., Odeberg, J., Kogner, P., Boman, H. G., Gudmundsson, G. H. (1995) FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis Proc. Natl. Acad. Sci. USA 92,195-199[Abstract/Free Full Text]
-
Gudmundsson, G. H., Agerberth, B., Odeberg, J., Bergman, T., Olsson, B., Salcedo, R. (1996) The human gene FALL-39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes Eur. J. Biochem. 238,325-332[Medline]
-
Chertov, O., Michiel, D. F., Xu, L., Wang, J. M., Tani, K., Murphy, W. J., Longo, D. L., Taub, D. D., Oppenheim, J. J. (1996) Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils J. Biol. Chem. 271,2935-2940[Abstract/Free Full Text]
-
Van Wetering, S., Mannesse-Lazeroms, S. P., Van Sterkenburg, M. A., Daha, M. R., Dijkman, J. H., Hiemstra, P. S. (1997) Effect of defensins on interleukin-8 synthesis in airway epithelial cells Am. J. Physiol. 272,L888-L896[Abstract/Free Full Text]
-
Van Wetering, S., Mannesse-Lazeroms, S. P., Dijkman, J. H., Hiemstra, P. S. (1997) Effect of neutrophil serine proteinases and defensins on lung epithelial cells: modulation of cytotoxicity and IL-8 production J. Leukoc. Biol. 62,217-226[Abstract]
-
Panyutich, A. V., Szold, O., Poon, P. H., Tseng, Y., Ganz, T. (1994) Identification of defensin binding to C1 complement FEBS Lett 356,169-173[Medline]
-
Prohaszka, Z., Nemet, K., Csermely, P., Hudecs, F., Mezo, G., Fust, G. (1997) Defensins purified from human granulocytes bind C1q and activate the classical complement pathway like the transmembrane glycoprotein gp41 of HIV-1 Mol. Immunol. 34,809-816[Medline]
-
van den Berg, R. H., Faber-Krol, M. C., van Wetering, S., Hiemstra, P. S., Daha, M. R. (1998) Inhibition of activation of classical pathway of complement by human neutrophil defensins Blood 92,3898-3903[Abstract/Free Full Text]
-
Solomon, S., Hu, J., Zhu, Q., Belcourt, D., Bennett, H. P. J., Bateman, A., Antakly, T. (1991) Corticostatic peptides J. Steroid Biochem. Mol. Biol. 40,391-398[Medline]
-
Zhu, Q., Hu, J., Mulay, S., Esch, F., Shimasaki, S., Solomon, S. (1988) Isolation and structure of corticostatin peptides from rabbit fetal and adult lung Proc. Natl. Acad. Sci. USA 85,592-596[Abstract/Free Full Text]
-
Lillard, J. W., Jr, Boyaka, P. N., Chertov, O., Oppenheim, J. J., McGhee, J. R. (1999) Mechanisms for induction of acquired host immunity by neutrophil peptide defensins Proc. Natl. Acad. Sci. USA 96,651-656[Abstract/Free Full Text]
-
Tani, K., Murphy, W. J., Chertov, O., Salcedo, R., Koh, C. Y., Utsunomiya, I., Funakoshi, S., Asai, O., Herrmann, S. H., Wang, J. M., Kwak, L. W., Oppenheim, J. J. (2000) Defensins act as potent adjuvants that promote cellular and humoral immune responses in mice to a lymphoma idiotype and carrier antigens Int. Immunol. 12,691-700[Abstract/Free Full Text]
-
Yang, D., Chen, Q., Schmidt, A. P., Anderson, G. M., Wang, J. M., Wooters, J., Oppenheim, J. J., Chertov, O. (2000) LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells J. Exp. Med. 192,1069-1074[Abstract/Free Full Text]
-
Agerberth, B., Charo, J., Werr, J., Olsson, B., Idali, F., Lindbom, L., Kiessling, R., Jomvall, H., Wigzell, H., Gudmundsson, G. H. (2000) The human anti-microbial and chemotactic peptides LL-37 and -defensins are expressed by specific lymphocyte and monocyte populations Blood 96,3086-3093[Abstract/Free Full Text]
-
Ganz, T. (1987) Extracellular release of anti-microbial defensins by human polymorphonuclear leukocytes Infect. Immun. 55,568-571[Abstract/Free Full Text]
-
Taub, D. D., Anver, M., Oppenheim, J. J., Longo, D. L., Murphy, W. J. (1996) T lymphocyte recruitment by interleukin-8 (IL-8). IL-8-induced degranulation of neutrophils releases potent chemoattractants for human T lymphocytes both in vitro and in vivo J. Clin. Invest. 97,1931-1941[Medline]
-
Porter, E. M., Liu, L., Oren, A., Anton, P. A., Ganz, T. (1997) Localization of human intestinal defensin 5 in Paneth cell granules Infect. Immun. 65,2389-2395[Abstract]
-
Svinarich, D. M., Wolf, N. A., Gomez, R., Gonik, B., Romero, R. (1997) Detection of human defensin 5 in reproductive tissues Am. J. Obstet. Gynecol. 176,470-475[Medline]
-
Zhao, C., Wang, I., Lehrer, R. I. (1996) Widespread expression of ß-defensin hBD-1 in human secretory glands and epithelial cells FEBS Lett 396,319-322[Medline]
-
McCray, P. B., Jr, Bentley, L. (1997) Human airway epithelia express a ß-defensin Am. J. Respir. Cell Mol. Biol. 16,343-349[Abstract]
-
Goldman, M. J., Anderson, G. M., Stolzenberg, E. D., Kari, U. P., Zasloff, M., Wilson, J. M. (1997) Human ß-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis Cell 88,553-560[Medline]
-
Singh, P. K., Jia, H. P., Wiles, K., Hesselberth, J., Liu, L., Conway, B. A., Greenberg, E. P., Valore, E. V., Welsh, M. J., Ganz, T., Tack, B. E., McCray, P. B., Jr (1998) Production of beta-defensins by human airway epithelia Proc. Natl. Acad. Sci. USA 95,14961-14966[Abstract/Free Full Text]
-
Valore, E. V., Park, C. H., Quayle, A. J., Wiles, K. R., McCrag, P. B., Jr, Ganz, T. (1998) Human ß-defensin-1: an anti-microbial peptide of urogenital tissues J. Clin. Invest. 101,1633-1642[Medline]
-
Krisanaprakornkit, S., Weinberg, A., Perez, C. N., Dale, B. A. (1998) Expression of the peptide antibiotic human ß-defensin 1 in cultured gingival epithelial cells and gingival tissue Infect. Immun. 66,4222-4228[Abstract/Free Full Text]
-
Mathews, M., Jia, H. P., Guthmiller, J. M., Losh, G., Graham, S., Johnson, G. K., Tack, B. F., McCray, P. B., Jr (1999) Production of beta-defensin anti-microbial peptides by the oral mucosa and salivary glands Infect. Immun. 67,2740-2745[Abstract/Free Full Text]
-
O’Neil, D. A., Porter, E. M., Elewaut, D., Anderson, G. M., Eckmann, L., Ganz, T., Kagnoff, M. F. (1999) Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium J. Immunol. 163,6718-6724[Abstract/Free Full Text]
-
Liu, L., Wang, L., Jia, H. P., Zhao, C., Heng, H. H. Q., Schutte, B. C., McCray, P. B., Jr, Ganz, T. (1998) Structure and mapping of the human ß-defensin HBD-2 gene and its expression at sites of inflammation Gene 222,237-244[Medline]
-
Bals, R., Wang, X., Wu, Z., Bafna, V., Zasloff, M., Wilson, J. M. (1998) Human ß-defensin 2 is a salt-sensitive peptide antibiotic expressed in human lung J. Clin. Invest. 102,874-880[Medline]
-
Hiratsuka, T., Nakazato, M., Date, Y., Ashitani, J., Minematsu, T., Chino, N., Matsukura, S. (1998) Identification of human ß-defensin-2 in respiratory tract and plasma and its increase in bacterial pneumonia Biochem. Biophys. Res. Commun. 249,943-947[Medline]
-
Nilsson, M. F., Sandstedt, B., Sorensen, O., Weber, G., Borregaad, N., Stahle-Backdahl, M. (1999) The human cationic anti-microbial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6 Infect. Immun. 67,2561-2566[Abstract/Free Full Text]
-
Frohm, M., Agerberth, B., Ahangari, G., Stahle-Backdahl, M., Liden, S., Wigzell, H., Gudmundsson, G. H. (1997) The expression of the gene coding for the anti-microbial peptide LL-37 is induced in human keratinocytes during inflammatory disorders J. Biol. Chem. 272,15258-15263[Abstract/Free Full Text]
-
Bals, R., Wang, X., Zasloff, M., Wilson, J. M. (1998) The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad anti-microbial activity at the airway surface Proc. Natl. Acad. Sci. USA 95,9541-9546[Abstract/Free Full Text]
-
Steinman, R. M. (1991) The dendritic cell system and its role in immunogenicity Annu. Rev. Immunol. 9,271-296[Medline]
-
Cella, M., Sallusto, F., Lanzavecchia, A. (1997) Origin, maturation and antigen presenting function of dendritic cells Curr. Opin. Immunol. 9,10-16[Medline]
-
Banchereau, J., Steinman, R. M. (1998) Dendritic cells and the control of immunity Nature 392,245-251[Medline]
-
Huang, H. J., Ross, C. R., Blecha, F. (1997) Chemoattractant properties of PR-39, a neutrophil antibacterial peptide J. Leukoc. Biol. 61,624-629[Abstract]
-
Pereira, H. A., Shafer, W. M., Pohl, J., Martin, L. E., Spitznagel, J. K. (1990) CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity J. Clin. Invest. 85,1468-1476
-
Chertov, O., Ueda, H., Xu, L. L., Tani, K., Murphy, W. J., Wang, J. M., Howard, O. M. Z., Sayers, T. J., Oppenheim, J. J. (1997) Identification of human neutrophil-derived cathepsin G and azurocidin/CAP37 as chemoattractants for mononuclear cells and neutrophils J. Exp. Med. 186,739-747[Abstract/Free Full Text]
-
Tani, K., Ogushi, F., Kido, H., Kawano, T., Kunori, Y., Kamimura, T., Cui, P., Sone, S. (2000) Chymase is a potent chemoattractant for human monocytes and neutrophils J. Leukoc. Biol. 67,585-589[Abstract]
-
Oppenheim, J. J., Zachariae, C. O., Mukaida, N., Matsushima, K. (1991) Properties of the novel proinflammatory supergene "intercrine" cytokine family Annu. Rev. Immunol. 9,617-648[Medline]
-
Murphy, P. M. (1994) The molecular biology of leukocyte chemoattractant receptors Annu. Rev. Immunol. 12,593-633[Medline]
-
Johansson, J., Gudmundsson, G. H., Rottenberg, M. E., Berndt, K. D., Agerberth, B. (1998) Conformation-dependent antibacterial activity of naturally occurring human peptide LL-37 J. Biol. Chem. 273,3718-3724[Abstract/Free Full Text]
-
Baggiolini, M. (1998) Chemokines and leukocyte traffic Nature 392,565-568[Medline]
-
Sallusto, F., Schaerli, P., Loetscher, P., Schaniel, C., Lenig, D., Mackay, C. R., Qin, S., Lanzavecchia, A. (1998) Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation Eur. J. Immunol. 28,2760-2769[Medline]
-
Sozzani, S., Allavena, P., D’Amico, G., Luini, W., Bianchi, G., Kataura, M., Imai, T., Yoshie, O., Bonecchi, R., Mantovani, A. (1998) Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properities J. Immunol. 161,1083-1086[Abstract/Free Full Text]
-
Yang, D., Howard, O. M. Z., Chen, Q., Oppenheim, J. J. (1999) Cutting edge: immature dendritic cells generated from monocytes in the presence of TGF-ß1 express functional C-C chemokine receptor 6 J. Immunol. 163,1737-1741[Abstract/Free Full Text]
-
Yang, D., Chen, Q., Stoll, S., Chen, X., Howard, O. M. Z., Oppenheim, J. J. (2000) Differential regulation of responsiveness to fMLP and C5a upon dendritic cell maturation: correlation with receptor expression J. Immunol. 165,2694-2702[Abstract/Free Full Text]
-
Su, S. B., Gong, W-H., Gao, J-L., Shen, W., Murphy, P. M., Oppenheim, J. J., Wang, J. M. (1999) A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells J. Exp. Med. 189,395-402[Abstract/Free Full Text]
-
Befus, A. D., Mowat, C., Gilchrist, M., Hu, J., Solomon, S., Bateman, A. (1999) Neutrophil defensins induce histamine secretion from mast cells: mechanisms of action J. Immunol. 163,947-953[Abstract/Free Full Text]
-
Tominaga, T., Fukata, J., Naito, Y., Funakoshi, S., Fujii, N., Imura, H. (1990) Effects of corticostatin-I on rat adrenal cells in vitro J. Endocrinol. 125,287-292[Abstract]
-
Zhu, Q., Solomon, S. (1992) Isolation and mode of action of rabbit corticostatic (antiadrenocorticotropin) peptides Endocrinology 130,1413-1423[Abstract]
-
Medzhitov, R., Janeway, C. A., Jr (1997) Innate immunity: the virtues of a nonclonal system of recognition Cell 91,295-298[Medline]
-
Lenschow, D. J., Walunas, T. L., Bluestone, J. A. (1996) CD28/B7 system of T cell costimulation Annu. Rev. Immunol. 14,233-258[Medline]
-
Ichinose, M., Asai, M., Imai, K., Sawada, M. (1996) Enhancement of phagocytosis by corticostatin I (CSI) in cultured mouse peritoneal macrophages Immunopharmacology 35,103-109[Medline]
-
Yamashita, T., Saito, K. (1989) Purification, primary structure, and biological activity of guinea pig neutrophil cationic peptides Infect. Immun. 57,2405-2409[Abstract/Free Full Text]
-
Echtenacher, B., Mannel, D. N., Hultner, L. (1996) Critical protective role of mast cells in a model of acute septic peritonitis Nature 381,75-77[Medline]
-
Malaviya, R., Ikeda, T., Ross, E., Abraham, S. N. (1996) Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF- Nature 381,77-80[Medline]
-
Sozzani, S., Longoni, D., Bonecchi, R., Luini, W., Bersani, L., D’Amico, G., Borsatti, A., Bussolino, F., Allavena, P., Mantovani, A. (1997) Human monocyte-derived and CD34+ cell-derived dendritic cells express functional receptors for platelet activating factor FEBS Lett 418,98-100[Medline]
-
Panyutich, A. V., Panyutich, E. A., Krapivin, V. A., Baturevich, E. A., Ganz, T. (1993) Plasma defensin concentrations are elevated in patients with septicemia or bacterial meningitis J. Lab. Clin. Med. 122,202-207[Medline]
-
Shiomi, K., Nakazato, M., Ihi, T., Kangawa, K., Matsuo, H., Matsukura, S. (1993) Establishment of radioimmunoassay for human neutrophil peptides and their increases in plasma and neutrophil in infection Biochem. Biophys. Res. Commun. 195,1336-1344[Medline]
-
Kirikae, T., Hirata, M., Yamasu, H., Kirikae, F., Tamura, H., Kayama, F., Nakatsuka, K., Yokochi, T., Nakano, M. (1998) Protective effects of a human 18-kilodalton cationic anti-microbial protein (CAP18)-derived peptide against murine endotoxemia Infect. Immun. 66,1861-1868[Abstract/Free Full Text]
-
Fearon, D. T., Locksley, R. M. (1996) The instructive role of innate immunity in the acquired immune response Science 272,50-54[Abstract]
This article has been cited by other articles:
|
|
|
|
 
O. Soehnlein, A. Zernecke, E. E. Eriksson, A. G. Rothfuchs, C. T. Pham, H. Herwald, K. Bidzhekov, M. E. Rottenberg, C. Weber, and L. Lindbom
Neutrophil secretion products pave the way for inflammatory monocytes
Blood,
August 15, 2008;
112(4):
1461 - 1471.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Di Nardo, K. Yamasaki, R. A. Dorschner, Y. Lai, and R. L. Gallo
Mast Cell Cathelicidin Antimicrobial Peptide Prevents Invasive Group A Streptococcus Infection of the Skin
J. Immunol.,
June 1, 2008;
180(11):
7565 - 7573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Gaudreault and J. Gosselin
Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice
J. Immunol.,
May 1, 2008;
180(9):
6211 - 6221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Simon, B. J. Kullberg, B. Tripet, O. C. Boerman, P. Zeeuwen, J. van der Ven-Jongekrijg, P. Verweij, J. Schalkwijk, R. Hodges, J. W. M. van der Meer, et al.
Drosomycin-Like Defensin, a Human Homologue of Drosophila melanogaster Drosomycin with Antifungal Activity
Antimicrob. Agents Chemother.,
April 1, 2008;
52(4):
1407 - 1412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Nagaoka, F. Niyonsaba, Y. Tsutsumi-Ishii, H. Tamura, and M. Hirata
Evaluation of the effect of human {beta}-defensins on neutrophil apoptosis
Int. Immunol.,
April 1, 2008;
20(4):
543 - 553.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Tran, P. Tran, K. Roberts, G. Osapay, J. Schaal, A. Ouellette, and M. E. Selsted
Microbicidal Properties and Cytocidal Selectivity of Rhesus Macaque Theta Defensins
Antimicrob. Agents Chemother.,
March 1, 2008;
52(3):
944 - 953.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Di Nardo, M. H. Braff, K. R. Taylor, C. Na, R. D. Granstein, J. E. McInturff, S. Krutzik, R. L. Modlin, and R. L. Gallo
Cathelicidin Antimicrobial Peptides Block Dendritic Cell TLR4 Activation and Allergic Contact Sensitization
J. Immunol.,
February 1, 2007;
178(3):
1829 - 1834.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ouhara, H. Komatsuzawa, H. Shiba, Y. Uchida, T. Kawai, K. Sayama, K. Hashimoto, M. A. Taubman, H. Kurihara, and M. Sugai
Actinobacillus actinomycetemcomitans Outer Membrane Protein 100 Triggers Innate Immunity and Production of {beta}-Defensin and the 18-Kilodalton Cationic Antimicrobial Protein through the Fibronectin-Integrin Pathway in Human Gingival Epithelial Cells
Infect. Immun.,
September 1, 2006;
74(9):
5211 - 5220.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Nagaoka, H. Tamura, and M. Hirata
An Antimicrobial Cathelicidin Peptide, Human CAP18/LL-37, Suppresses Neutrophil Apoptosis via the Activation of Formyl-Peptide Receptor-Like 1 and P2X7.
J. Immunol.,
March 1, 2006;
176(5):
3044 - 3052.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Tokumaru, K. Sayama, Y. Shirakata, H. Komatsuzawa, K. Ouhara, Y. Hanakawa, Y. Yahata, X. Dai, M. Tohyama, H. Nagai, et al.
Induction of Keratinocyte Migration via Transactivation of the Epidermal Growth Factor Receptor by the Antimicrobial Peptide LL-37
J. Immunol.,
October 1, 2005;
175(7):
4662 - 4668.
[Abstract]
[Full Text]
[PDF]
|
|
|
TOP
ABSTRACT
INTRODUCTION
