Published online before print March 27, 2008
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Center of Excellence in Vascular Biology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
1Correspondence: Center of Excellence in Vascular Biology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, New Research Building 7520, Boston, MA 02115, USA. E-mail: tmayadas{at}rics.bwh.harvard.edu
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Rs and the CD18 integrin Mac-1 in IC-mediated neutrophil adhesion. Furthermore, ICAM-1, a major Mac-1 ligand constitutively expressed on unactivated endothelium, significantly contributed to this process. These data suggest that TNF priming promotes FcR interaction with intravascular ICs, leading to the binding of Mac-1 to ICAM-1 and subsequent neutrophil arrest.
Key Words: adhesion molecules • Fc receptors • cytokines • cell trafficking
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Leukocyte adhesion receptors on neutrophils and the endothelium, such as the selectins, β2 integrins, and members of the IgG superfamily (ICAM family members), have been implicated in neutrophil recruitment during an inflammatory response. However, an understanding of the molecular requirements for neutrophil recruitment in the context of IC deposition is still in its infancy. FcRs, receptors for IgG-containing ICs, contribute to the pathogenesis of several immune-mediated diseases in mice, including nephrotoxic nephritis, lupus nephritis, autoimmune skin diseases, and arthritis [2
, 3
]. In all of these models, Fc deficiency is associated with a reduction in neutrophil accumulation. Neutrophil recruitment in these models may result from the engagement of ICs by FcR on mast cells and macrophages, which leads to the release of endothelial-activating agonists chemokines and cytokines. Subsequent endothelial cell activation, IC-mediated activation of complement, and subsequent generation of anaphylatoxins C3a and C5a may mobilize neutrophils, and/or FcRs on neutrophils may directly facilitate recruitment to deposited ICs [1
, 4
, 5
]. Mice deficient in the leukocyte-specific CD18 integrin Mac-1 are protected from IgG-mediated diseases such as acute anti-glomerular basement membrane nephritis and bullous pemphigoid [6
, 7
]. Mac-1 deficiency in these FcR-dependent models is also associated with reduced neutrophil accumulation [6
, 7
]. This may be attributed to compromised FcR-mediated adhesion, as some FcR functions rely on Mac-1-dependent signal transduction [7
8
9
]. It is also possible that the absence of Mac-1 interaction with its ligand complement fragment C3bi may limit neutrophil cytotoxicity and thus, curb subsequent neutrophil accumulation, and/or the absence of Mac-1 interaction with ICAM-1 on the activated endothelium may mediate neutrophil recruitment. Thus, although FcR or Mac-1 deficiency results in reductions in neutrophil accumulation in various IgG-mediated models of disease, the mechanisms responsible for neutrophil recruitment remain largely undefined.
Cytokines such as TNF, elevated in autoimmune diseases [10 ], not only activate the endothelium but also have the potential to "prime" neutrophil responses. The definition of priming is that it itself does not result in the desired response, but the process significantly amplifies neutrophil responsiveness to subsequent external stimuli. This may serve to augment the inflammatory response [11 12 13 ]. Priming of neutrophils, which occurs within seconds/minutes, likely precedes cytokine-mediated activation of the endothelium, which principally results from the transcriptional up-regulation of leukocyte adhesion receptors and cytokines/chemokines, a process that occurs over hours. Priming likely represents a mechanism to localize neutrophil effector functions to sites of inflammation, thus limiting the damaging potential of neutrophils. The failure to limit cell priming may contribute to disease pathogenesis, yet definitive evidence that priming enhances neutrophil responses in vivo remains an elusive goal in the field.
Here, we examined the contribution of neutrophil priming to neutrophil recruitment to intravascularly deposited ICs in vivo and evaluated the potential contributions of FcRs and Mac-1 on neutrophils as well as the endothelial ligand for Mac-1, ICAM-1, to this process. Our experimental approach included the analysis of knockout mouse strains and neutrophil reconstitution in an in vivo model of IC deposition in the exteriorized cremaster microcirculation that is amenable to intravital microscopy (IVM).
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
chain–/– on a C57Bl/6 strain (backcrossed 12 generations) was from Taconic (Germantown, NY, USA), and ICAM-1–/– on a C57Bl/6 strain (backcrossed 10 generations) was from The Jackson Laboratory (Bar Harbor, ME, USA). Mac-1–/– [14
], backcrossed eight generations to C57Bl/6, was bred and maintained in our animal facility. All mice were housed in a virus antibody-free facility at Longwood Medical Research Center, Brigham and Women’s Hospital (Boston, MA, USA). The Institutional Animal Care and Use Committee approved the experimental protocols used in this study.
Preparation and administration of preformed, soluble ICs (sICs)
sICs were made using BSA/polyclonal rabbit anti-BSA (Sigma-Aldrich, St. Louis, MO, USA) as described previously [5
] and injected into the cannulated femoral artery [15
]. IC deposition was verified as described previously [5
].
Preparation and injection of bone marrow-derived neutrophils (BMN)
BMN were isolated from donor animals using three-layer Percoll-gradient centrifugation (75%, 65%, 55%) [16
], pooled, and counted. Isolated neutrophils were stained using the fluorophore 5-chloromethylfluorescein diacetate (CMFDA; Celltracker, Carlsbad, CA, USA), according to the manufacturer’s protocol. After staining, 2.5 x 107 cells were washed, treated with TNF (200 ng/ml recombinant murine TNF-
for 15 min), washed again, and injected into the cannulated femoral artery [15
] after sIC injection.
Flow cytometry of isolated BMN
Cells (2x106) for each sample were washed with PBS, then TNF-treated in 100 µL PBS, or left untreated. After 15 min, the cells were washed with PBS-0.1% BSA and labeled with CD11b-allophycocyanin (APC) antibody (eBioscience, San Diego, CA, USA), CD32/CD16-FITC antibody (BD PharMingen, San Diego, CA, USA), or matching isotypes. A second set of cells was similarly prepared but stained with propidium iodide (BD PharMingen) and Gr-1-FITC antibody (BD PharMingen). The samples were analyzed with a BD flow cytometer (BD FACSCalibur flow cytometer, four-color).
To assess potential differences in Mac-1 surface expression between peripheral blood neutrophils (PBN) and BMN, 2.5 x 107 CMFDA-stained BMN were injected into wild-type (WT) mice, and their peripheral blood was collected 45 min after injection of BMN. Following lysis of RBCs with repetitive 4°C H2O washes, cells were stained with Gr-1-PE (BD PharMingen) and CD11b-APC (eBioscience) or appropriate isotype controls.
IVM
Leukocyte recruitment in cremaster muscle venules was evaluated in mice within 45 min of a single i.v. injection of unlabeled ICs or controls. Mice (n=5 per group) were anesthetized with ketamine (90 mg/kg), xylazine (18 mg/kg), and atropine (0.24 mg/kg). A femoral artery line was placed, which took 15 min. sICs were injected through the femoral line prior to cremaster surgery. The cremaster was prepared as described previously [14
] and took 15–20 min. A reflecting mirror was positioned underneath the cremaster for reflective light oblique transillumination (RLOT) [17
]. The mouse was transferred to an upright saline immersion intravital microscope (Mikron Instruments, Glendale, CA, USA). In experiments with neutrophil reconstitution, BMN were injected through the femoral line and allowed to circulate and adapt for 15 min before recording. Fluorescent signals were generated by a xenon lamp, video-synchronized with a stroboscope (model 315-T, Colorado video), and detected using a silicon-intensified camera (Hamamatsu Photonics, Japan). Signals were transferred through an on-line image processor (Argus 20, Hamamatsu Photonics, Japan). Transilluminated light (RLOT) was captured by a charged-coupled device camera (Sony, Japan). Video signals from both cameras were digitized (Moviebox DV, Pinnacle Systems, Inc., Mountain View, CA, USA) and stored on a standard personal computer. The stored video files were then analyzed using ImageJ [National Institutes of Health (NIH), Bethesda, MD, USA] with Quicktime plug-in.
Four to five venules were analyzed over a 20-min time period. During the experiment, the cremaster muscle was immersed with warmed, normal saline solution (0.9%). The use of normal saline instead of lactated Ringer’s solution or Krebs Henseleit buffer had no detectable effect on leukocyte behavior (data not shown). At completion of the IVM experiment, blood was sampled from the retro-orbital plexus and collected into EDTA containing Eppendorf tubes to obtain total and differential leukocyte counts.
Peripheral leukocyte counts
Total leukocyte counts were determined with a Coulter counter (Coulter Electronics, Fullerton, CA, USA). Differential counts (100 cells) were performed on Wright-Giemsa’s stained blood smears.
Analysis of intravital microscopy data
Leukocyte rolling flux and BMN rolling flux were defined as the number of leukocytes rolling past a perpendicular point in a vessel over 60 s. These were converted to the leukocyte rolling flux fraction (of total leukocyte flux) and BMN rolling flux fraction, as described [18
]. Rolling cell flux fraction represents the percentage of rolling cells of the total flux (calculated from the systemic total leukocyte count) of leukocytes passing through the vessel. BMN rolling flux fraction of local BMN flux describes the percentage of rolling BMN to noninteracting BMN in the vessels of interest. The mean blood flow velocity (Vmean) was calculated as centerline velocity/1.6, and wall shear rate was calculated as 8 x (Vmean/venule diameter) [19
, 20
]. Leukocyte rolling velocities were measured by tracking single leukocytes (10/venule) over several frames and calculating distance moved per unit time (µm/s). Adherent leukocytes were defined as cells remaining stationary for 30 s and were expressed per mm2 venule.
Statistical analysis
IVM data were presented as means ± SEM or median ± SEM if nonparametric. Statistical analysis was performed with Sigma Stat (SPSS Science Inc., Chicago, IL, USA). Statistical significance of differences between groups was tested with a Student’s t-test or a one-way ANOVA where appropriate. A multiple-comparison procedure was performed using the Holm-Sidak method. Statistical significance was accepted at P < 0.05.
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Rs as assessed by flow cytometry. Treatment with murine TNF for 15 min doubled the surface expression of Mac-1 (Fig. 1A
) but did not alter FcR expression levels compared with vehicle-treated BMN (Fig. 1A)
. The lowest TNF dose to achieve the maximum surface expression of Mac-1 on BMN was 200 ng/ml (Fig. 1B)
. This TNF dose was henceforth used to prime BMN prior to their injection into recipient mice as described below. BMN from Fc–/– mice exhibited Mac-1 surface expression that was similar to WT mice and likewise, inducible with TNF treatment (Fig. 1B)
. As expected, Mac-1 expression was undetectable in BMN from Mac-1–/– mice (Fig. 1B)
.
 View larger version (69K): [in a new window] |
Figure 1. Effect of TNF priming on neutrophil FcR and Mac-1 expression and IC-induced adhesion in vivo. (A) Flow cytometric analysis of FcRII/III (left panel) and Mac-1 (CD11b) expression (right panel) in PBN (dotted line), BMN (gray line), and 200 ng/mL TNF-treated BMN (black line). (B) Mac-1 (CD11b) surface expression in wild-type BMN following stimulation with the indicated doses of TNF (ng/ml) is shown (left panel). The lowest TNF concentration to achieve maximum Mac-1 expression was 200 ng/mL. (Right panel) Mac-1 expression, before (–) and after (+) 200 ng/ml TNF treatment, was evaluated in Fc deficient (–/–) and in Mac-1-deficient neutrophils, which served as a control for nonspecific staining of the antibody. Histograms show expression levels after gated acquisition, with the gate being set to side-scatter/forward-scatter characteristics of neutrophils combined with a high Gr-1 signal. (C) Analysis of endogenous leukocytes and fluorophore-labeled, TNF-primed BMN by IVM. Mice given sICs or PBS alone (sIC, –/+), were i.v.-injected with fluorophore-labeled, naïve or TNF-treated BMN (BMN/TNF, –/+), and the rolling velocity and adhesion of the endogenous, unlabeled leukocytes (left two panels) and fluorophore-labeled, adoptively transferred BMN (right two panels) were evaluated. Adherent cells are expressed as cells per mm2 of the endothelial surface assuming cylindrical geometry of the vessel. *, P < 0.05; n = 5 per group. (Bottom) Representative pictures of a cremaster postcapillary venule of a WT recipient i.v. given TNF-primed BMN in bright-field illumination (left panel), stroboscopic FITC illumination (middle panel), and a merged picture of bright-field and FITC illumination (right panel) are shown. Black arrowheads identify endogenous leukocytes, and white arrowheads point to fluorophore-labeled BMN.
|
Neutrophil recruitment to intravascular ICs is significantly reduced in primed Fc–/– BMN
We have shown previously that FcR deficiency in mice abrogates IC-induced, slow rolling on P-selectin and subsequent adhesion [5
]. Here, we directly examined the role of activating FcRs on neutrophils in recruitment of TNF-primed neutrophils. Fc chain-deficient mice (Fc–/–) lack all activating FcRs but retain expression of the inhibitory FcRIIB. Consistent with this, flow cytometry analysis of Fc–/– BMN using an antibody that recognizes all FcRs revealed a 60% reduction in FcR expression. The remaining fluorescence intensity was the result of retained FcRIIB expression (data not shown), as previously reported [22
]. BMN isolated from WT and Fc–/– mice were labeled, TNF-treated, and injected into WT recipients given sIC. The rolling BMN flux fraction was similar in mice reconstituted with WT or Fc–/– BMN. The slow rolling velocity characteristically observed in the presence of ICs was similar in TNF-treated Fc–/– BMN and WT BMN, which may be attributed to the retained FcRIIB expression in Fc chain–/– BMN (Fig. 2
); eliminating activating FcRs and FcRIIB voids the slow rolling in response to intravascular sIC [5
]. We also cannot rule out the possibility that TNF-treated FcR–/– BMN may have alternate mechanisms for promoting slow rolling compared with PBN. Importantly, firm adhesion of TNF-treated Fc–/– BMN was severely altered compared with similarly treated WT BMN (Fig. 2)
. Endogenous neutrophils in the WT hosts reconstituted with Fc–/– BMN efficiently adhered to the vessel wall of mice (data not shown), which demonstrates that IC deposition was adequate for promoting BMN adhesion. Thus, FcRs on neutrophils play an important role in the interaction of TNF-primed neutrophils with the vessel wall.
 View larger version (25K): [in a new window] |
Figure 2. Contribution of neutrophil FcR to IC-induced neutrophil adhesion. Fluorophore-labeled, TNF-treated WT (Fc, +/+) or Fc chain-deficient (Fc, –/–) BMN were injected into WT recipients given sIC. The left panel shows the rolling velocity of injected BMN; the middle panel, BMN rolling flux fraction; and the right panel, the number of adherent BMN. *, P < 0.05; n = 5 per group.
|
 View larger version (14K): [in a new window] |
Figure 3. Analysis of Mac-1-deficient mice given sICs. Mac-1 deficient (–/–) mice and WT counterparts (+/+) were injected with sICs and prepared for IVM. Leukocyte rolling velocity, rolling cell flux fraction, and the number of adherent cells are shown. *, P < 0.05; n = 5 per group.
|
 View larger version (17K): [in a new window] |
Figure 4. IC-induced leukocyte recruitment is reduced in ICAM-1-deficient mice (–/–), which were analyzed following injection of sIC. For purposes of comparison, the data for WT mice are presented from Figure 3
. Leukocyte rolling velocity, rolling cell flux fraction, and adherent cells are depicted. *, P < 0.05; n = 5 per group.
|
 View larger version (39K): [in a new window] |
Figure 5. Analysis of the contribution of endothelial ICAM-1 and neutrophil Mac-1 to IC-induced adhesion of TNF-primed neutrophils. (A) Vehicle- or TNF-treated BMN were injected into ICAM-1-deficient recipient (REC) mice (ICAM-1Rec, –/–) given sICs. For purposes of comparison, the dataset for the WT group (referred to here as ICAM-1Rec, +/+) is duplicated from Figure 1B
. *, P < 0.05; n = 5 per group. (B) WT (WTRec, +/+) mice injected with sICs were prepared for IVM, and TNF-primed, fluorophore-labeled WT (Mac-1, +/+) or Mac-1-deficient (Mac-1, –/–) BMN were delivered i.v. *, P < 0.05; n = 5 per group. (C) ICAM-1–/– mice (ICAM-1Rec, –/–) were injected with sICs and labeled TNF-primed Mac-1+/+ or Mac-1–/– BMN. *, P < 0.05; n = 5 per group.
|
–/– BMN reconstitution of WT mice (Fig. 2)
. Thus, the study of endogenous Mac-1–/– neutrophils and TNF-treated Mac-1–/– BMN suggests that this β2 integrin on neutrophils plays an important role in regulating IC-induced neutrophil adhesion. Next, we specifically addressed whether endothelial ICAM-1 interactions with Mac-1 are contributing to the observed IC-mediated responses. TNF-primed WT or Mac-1–/– BMN were injected into ICAM-1–/– recipient mice given sICs, and leukocyte rolling velocity, flux fraction, and adhesion were measured. Adhesion of WT neutrophils in ICAM-1–/– recipients was similar to that observed in the group of animals analyzed in Figure 5A as expected. A further, significant decrease in firm adhesion was observed in ICAM-1–/– recipients receiving Mac-1–/– BMN (Fig. 5C) . Indeed, ICAM-1–/– recipient mice given Mac-1-deficient BMN exhibit a greater decrease in adhesion (73%) compared with those given WT BMN (42%) or when WT recipient mice are given Mac-1-deficient BMN (53%). This suggests that the adhesion observed following IC deposition is not exclusively the result of Mac-1 interaction with ICAM-1 but includes the interaction of these receptors with other ligands.
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Rs in mice abrogates these processes [5
]. Here, our study used knockout mice and neutrophil reconstitution approaches to show that TNF priming significantly increased neutrophil adhesion only in the context of intravascular ICs and demonstrates a critical role for neutrophil-activating FcRs and a CD18 integrin, Mac-1, in recruitment of TNF-primed neutrophils to intravascularly deposited ICs. Furthermore, endothelial ICAM-1, which is a major ligand for neutrophil Mac-1, played an essential role in IC-mediated neutrophil arrest.
The paradigm for leukocyte recruitment during an inflammatory response has been primarily established from studies of IVM following injection of cytokines in tissues of interest. Unlike the requirement in these models for cytokine-inducible endothelial adhesion molecules and chemokines, neutrophil recruitment following strictly intravascular IC deposition appears not to require overt endothelial cell activation. Instead, it relies on the presence of constitutively present adhesion receptors such as neutrophil FcRs and Mac-1 and endothelial ICAM-1, and potentially "priming" stimuli such as TNF. TNF is a pleiotropic cytokine shown to activate endothelial cells and neutrophils. Previous analyses of leukocyte recruitment have most often been conducted several hours following intrascrotal injections of TNF and/or other inflammatory mediators. This leads to endothelial activation and adhesion receptor and chemokine expression that promote robust leukocyte-vessel wall interactions [24
], which precludes the analyses of the role of TNF priming of neutrophils in neutrophil recruitment. Our studies show for the first time that neutrophil priming has relevance in vivo and in particular, contributes to leukocyte recruitment.
The increase in adhesion of TNF-primed BMN in response to intravascular ICs provides strong evidence that TNF can modulate FcR function in vivo and that this has consequences for leukocyte recruitment. Previous studies show that inflammatory mediators such as C5a, TNF, and IFN- can up-regulate FcRIIIs on monocytes and macrophages [25
26
27
]. However, FcR surface expression on neutrophils did not change following TNF treatment. The mechanism for enhanced adhesion could thus be related to TNF-induced changes in FcR affinity for ligand. In support of this, TNF treatment of human neutrophils did not increase surface expression of FcRs but induced their clustering leading to cytoskeletal rearrangement and subsequent neutrophil binding to IgG in vitro [28
]. Similarly, stimulation with the neutrophil chemoattractant fMLP significantly increased FcR engagement of IC-opsonized targets in vitro [29
]. Thus, although FcRs are capable of binding ICs, their affinity for ligand may be increased by exogenous priming/activating stimuli, in a manner analogous to that described for β2 integrins [8
]. Indeed, FcR affinity modulation may represent another layer of regulation of FcR function in addition to those already described. FcR function is regulated by cytokine-induced increase in their surface expression levels. Cytokine regulation of IgG class-switching indirectly regulates FcR function activity as FcRs are known to differentially engage specific IgG isotypes [3
].
Previous studies suggest that the mechanism of TNF-induced priming may be an increase in receptor expression or post-receptor events [30 , 31 ]. For example, TNF priming of the fMLP-mediated oxidative burst in neutrophils may be attributed to TNF-induced increases in cell surface expression of fMLP receptors and/or increased phosphorylation of the NADPH oxidase phox components [32 ]. In our studies, TNF priming increased Mac-1 surface expression (Fig. 1A and 1B) [28 ], but this itself did not enhance the number of neutrophils adherent to the vessel wall (Fig. 1C) . The increase in adhesion was only evident when a secondary stimulus, ICs, was present within the vasculature (Fig. 1C) . TNF priming likely modulates more than Mac-1 expression to promote adhesion, as an increase in integrin expression alone is not sufficient for ligand binding. Additional changes in integrin affinity and/or stimulation of downstream signaling pathways (e.g., protein kinase C-dependent pathways) are needed. Regardless of the mechanism of TNF priming, our studies do show that TNF priming is relevant in the context of IC- mediated neutrophil recruitment. This is important data, as although we assume that neutrophil priming plays a physiological role in inflammatory responses, evidence of this in vivo has not been presented previously.
Crosstalk between FcRs and Mac-1 has been implicated in IC-induced neutrophil adhesion in vitro. Similarly to GPCRs, FcRs switch Mac-1 from a low- to a high-affinity/avidity state that binds ligands [8
, 9
, 33
]. Here, FcR engagement of intravascular ICs may trigger the activation of Mac-1 and subsequent binding to its ligand ICAM-1 present on the endothelium. At a molecular level, this may occur through FcR-induced phosphorylation of L-plastin, a leukocyte-specific, actin-bundling protein that is involved in Mac-1 activation [34
] and/or Mac-1 clustering [33
]. Mac-1 is critical for establishing shear-resistant contacts with the ICs [4
, 7
]. We propose that Mac-1 interaction with ICAM-1 strengthens the adhesive contact initiated by FcR/IC interactions and that this is required for firm arrest.
Our studies also suggest that Mac-1 and ICAM-1 interactions with other binding partners may contribute to IC-induced adhesion, as a deficiency in both leads to a greater defect in neutrophil adhesion than either one alone. Notably, elimination of neutrophil Mac-1 and endothelial ICAM-1 basically abrogates adhesion, suggesting that these two proteins are responsible for all detectable IC-induced adhesive activity of TNF-primed neutrophils. Our finding that ICAM-1 on the unstimulated endothelium supports IC-mediated neutrophil adhesion is surprising, as there are limited data about the contribution of ICAM-1 on "unactivated" endothelium to neutrophil recruitment [35 ]. Complement activation by ICs could also generate a Mac-1 ligand, complement C3 that could support cell adhesion. However, although complement C1q activated by the classical complement pathway is required for permeability-induced IC deposition, complement C3 does not play a role in neutrophil recruitment to intravascular ICs in this model [5 ].
In conclusion, our analyses revealed a role for TNF priming of neutrophils in selectively enhancing neutrophil adhesion to intravascular ICs. Priming of neutrophil functions by cytokines might contribute to the pathology of IgG-mediated disease. For example, in transfusion-related acute lung injury, characterized by antibody- and neutrophil-priming stimuli, cytokine priming of neutrophil functions may enhance disease severity [36
]. Importantly, we provided evidence that FcR interaction with ICs leads to Mac-1 interaction with ICAM-1 on the endothelium, steps that are required for firm neutrophil arrest in the context of intravascular IC deposition. Our finding that the molecular components required for IC-induced recruitment are constitutively present in the vascular system (i.e., FcR, Mac-1, and ICAM-1) suggests that they may constitute a potent pathway of neutrophil recruitment in the absence of overt inflammation. This could represent an early pathogenic event in IC-induced disease characterized by circulating ICs such as vasculitides, systemic lupus erythematosus, and some forms of glomerulonephritis.
Received June 21, 2007; revised February 19, 2008; accepted February 20, 2008.
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
receptors in phagocytes Curr. Opin. Hematol. 5,16-21[Medline] receptors: old friends and new family members Immunity 24,19-28[CrossRef][Medline] RIII mediates neutrophil recruitment to immune complexes. a mechanism for neutrophil accumulation in immune-mediated inflammation Immunity 14,693-704[CrossRef][Medline] receptors mediate subsequent neutrophil recruitment J. Exp. Med. 200,835-846 receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis J. Exp. Med. 186,1853-1863 receptors and complement receptors in phagocytes van de Winkel, J. Capel, P. eds. Human IgG Fc Receptors ,149-163 R. G. Landes Austin, TX, USA. Mβ2-integrin glycoprotein Crit. Rev. Immunol. 20,197-222[Medline] in anti-neutrophil cytoplasmic antibody-associated vasculitis? Lessons from other chronic inflammatory diseases J. Am. Soc. Nephrol. 17,1243-1252 chain deletion results in pleiotrophic effector cell defects Cell 76,519-529[CrossRef][Medline]-induced inflammation J. Immunol. 171,6105-6111Rs in immune complex-induced lung disease J. Clin. Invest. 110,1823-1830[CrossRef][Medline] of human neutrophil NADPH-oxidase activity induced by anti-proteinase-3 or anti-myeloperoxidase antibodies J. Leukoc. Biol. 80,1424-1433 regulates expression of receptors for formyl-methionyl-leucyl-phenylalanine, leukotriene B4, and platelet-activating factor. Dissociation from priming in human polymorphonuclear neutrophils J. Immunol. 147,3842-3847[Abstract] induces phosphorylation of p47(phox) in human neutrophils: partial phosphorylation of p47phox is a common event of priming of human neutrophils by TNF- and granulocyte-macrophage colony-stimulating factor J. Immunol. 171,4392-4398-receptors induce Mac-1 (CD11b/CD18) mobilization and accumulation in the phagocytic cup for optimal phagocytosis J. Biol. Chem. 278,45720-45729This article has been cited by other articles:
 |
|
 |
|
  A. E. Morris, H. D. Liggitt, T. R. Hawn, and S. J. Skerrett Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia Am J Physiol Lung Cell Mol Physiol, December 1, 2009; 297(6): L1112 - L1119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. N. Mayadas, G. C. Tsokos, and N. Tsuboi Mechanisms of Immune Complex-Mediated Neutrophil Recruitment and Tissue Injury Circulation, November 17, 2009; 120(20): 2012 - 2024. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
