| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Published online before print December 9, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
* Laboratory of Cellular and Molecular Immunology, Department of Molecular and Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Brussels, Belgium; Departments of
Veterinary Medicine and
¶ Microbiology, Laboratory of Immunology, Institute for Tropical Medicine, Antwerp, Belgium;
Department of Molecular Biomedical Research, Vlaams Interuniversitair Instituut voor Biotechnologie, Ghent University, Belgium;
Department of Immunology, University of Cape Town, Groote Schuur Hospital, South Africa; and
|| Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
1 Correspondence: Cellular and Molecular Immunology Unit, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Building E, Level 8, Pleinlaan 2, B-1050 Brussels, Belgium. E-mail: Geert.Raes{at}vub.ac.be
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Key Words: subtracted cDNA • type II cytokines • alveolar macrophages • monocytes
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
(IFN-), are the best-studied macrophage subsets. They are important components of host defense against various pathogens and are typically characterized by the secretion of nitric oxide (NO) and proinflammatory cytokines. Type II cytokines, such as interleukin (IL)-4 and IL-13, antagonize caMF and induce the development of alternatively activated macrophages (aaMF), exhibiting among others, enhanced expression of the macrophage mannose receptor (MMR) [3
]. Moreover, in aaMF, the production of NO and L-citrulline from L-arginine by inducible NO synthase is suppressed. Instead, aaMF are characterized by an alternative metabolic pathway of L-arginine, catalyzed by arginase 1, converting L-arginine to L-ornithine and urea [4
]. Functionally, aaMF are considered to secure the balance between pro- and anti-inflammatory reactions during type I, cytokine-driven, inflammatory responses and to be involved in angiogenesis and wound healing [1
]. Conversely, the association of aaMF with type II, cytokine-controlled, inflammatory diseases [5
] suggests that under these circumstances, aaMF may support the development of clinical disease. To gain better insight into their multiple, functional properties in vivo and their contribution to disease pathogenesis, the molecular repertoire of aaMF needs to be better characterized. In particular, additional and reliable markers for in situ analysis of aaMF as well as for flow cytometric analysis of isolated cells are required [2
]. From a subtracted cDNA library between murine aaMF and caMF, elicited in vivo during trypanosome infections, we recently identified the cysteine-rich secreted protein, found in inflammatory zone 1 (FIZZ1) and the secretory lectin chitinase 3-like 3/4 (also known as Ym) as markers for aaMF. We documented that FIZZ1 and Ym were strongly induced in aaMF as compared with caMF during trypanosome infections, up-regulation of these genes was dependent on IL-4 in vivo, and expression of these genes was induced by treatment of cultured macrophages with IL-4 or IL-13 in vitro [6 ]. In addition, FIZZ1 and Ym were found to be expressed at high levels in aaMF recruited to the peritoneum after implanting the Brugia malayi nematode [7 ]. Moreover, expression of both of these genes was described to be up-regulated during type II, cytokine-controlled, allergic pulmonary inflammation [8 , 9 ]. In this report, we document the identification from our subtracted library of new aaMF-associated markers, belonging to the macrophage galactose-type C-type lectin (MGL) surface receptor gene family. A comparative expression analysis of these novel markers along with a number of established aaMF markers were performed in a range of in vitro and in vivo settings.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
KO [12
] BALB/c were inoculated i.p. with 10 nonbudding Toi strain Taenia crassiceps metacestodes as described [13
]. Peritoneal macrophages were isolated via plastic adherence of peritoneal exudate cells (PEC), as described earlier [6
]. Briefly, 6 x 106 PEC were dispensed in six-well tissue-culture dishes (Falcon, BD Biosciences, San Jose, CA) in 3 ml RPMI-1640 medium supplemented with 10% heat-inactivated fetal calf serum (FCS), 5 x 10–5 M 2-mercaptoethanol, 2 mM L-glutamine, 100 IU/ml penicillin, 100 µg/ml streptomycin, and 0.1 mM nonessential amino acids (all from Gibco-Invitrogen Life Technologies, Carlsbad, CA), and incubated at 37°C for 3 h in a humidified incubator with 5% CO2 in air. Nonadherent cells were washed away with RPMI 1640 prewarmed at 37°C. As an alternative to plastic adherence, PEC were stained for 20 min at 4°C using fluorescein isothiocyanate (FITC)-conjugated anti-CD11b (PharMingen, BD Biosciences, San Diego, CA) and phycoerythrin (PE)-conjugated anti-F4/80 (Serotec, Oxford, UK), after which the double-positive cells were purified via fluorescence-activated cell sorting (FACS) on a FACSVantage SE flow cytometer (Becton Dickinson, Sunnyvale, CA). Similar results were obtained upon expression analysis in peritoneal macrophages isolated via plastic adherence or FACS. Allergic airway inflammation was induced in C57Bl/6 mice as described [14 ]. Briefly, mice were sensitized by a single i.p. injection of 10 mg ovalbumin (OVA; grade V, Sigma Chemical Co., St. Louis, MO), adsorbed to 1 mg Al(OH)3 (alum). On day 14, the sensitized mice were exposed to seven daily OVA aerosols (1%; 30 min) using a Jet nebulizer (Vital Signs, Totowa, NJ). Bronchoalveolar lavage was performed 24 h after the last challenge as described [14 ] with 3 x 1 ml Ca2+- and Mg2+-free Hanks’ balanced saline solution (Life Technologies), supplemented with 0.05 mM EDTA. Alveolar macrophages were first enriched via a MiniMACS separator (Miltenyi Biotec, Bergisch Gladbach, Germany) using Miltenyi MicroBeads and CD11c antibodies (PharMingen), followed by FACS of high autofluorescent cells.
In vitro cytokine treatment of murine macrophages and human monocytes
The plastic-adherent population of PEC from BALB/c mice, injected i.p. with 3 ml thioglycollate broth (BioMérieux, Marcy l’ Etoile, France) 4 days prior to collection, was cultured in the presence of 100 IU/ml mouse recombinant (mr)IL-4 (PharMingen) or 100 IU/ml mrIFN- (PharMingen) for 48 h.
Human peripheral blood monocytes were prepared as described previously [15
]. Briefy, peripheral blood mononuclear cells isolated from donor buffy coats were separated into lymphocyte- and monocyte-enriched fractions by counter-flow elutriation. The pooled monocyte-enriched fractions were treated with sheep erythrocytes, after which the E-rosette-negative fraction was obtained using density gradient separation. Cells (6x106) were dispensed in six-well tissue-culture dishes (Falcon) in 3 ml RPMI-1640 medium supplemented with 10% heat-inactivated FCS, 2 mM L-glutamine, 100 IU/ml penicillin, and 100 µg/ml streptomycin (Gibco-Invitrogen Life Technologies) and incubated in vitro for 3 days with human (h)rIFN- (1000 IU/ml) or hrIL-4 (15 ng/ml) at 37°C in a humidified incubator containing 5% CO2 in air.
RNA extraction and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis
Total RNA was prepared using Trizol reagent (Gibco-Invitrogen Life Technologies), and 1 µg total RNA was reverse-transcribed using oligo(dT) and Superscript II RT (Gibco-Invitrogen Life Technologies) following the manufacturer’s recommendations. Quantitative real-time PCR was performed in an iCycler (Bio-Rad, Hercules, CA), with Bio-Rad iQ SYBR Green supermix. Primers and PCR conditions were as described before for mouse FIZZ1 and Ym [6
] and for human alternative macrophage activation-associated CC chemokine 1 (AMAC-1) [16
]. Other primers used were: mouse ribosomal protein S12 sense (5'-CCTCGATGACATCCTTGGCCTGAG-3'), mouse ribosomal protein S12 antisense (5'-GGAAGGCATAGCTGCTGGAGGTGT-3'), mMGL1 sense (5'-ATGATGTCTGCCAGAGAACC-3'), mMGL1 antisense (5'-ATCACAGATTTCAGCAACCTTA-3'), mMGL2 sense (5'-GATAACTGGCATGGACATATG-3'), mMGL2 antisense (5'-TTTCTAATCACCATAACACATTC-3'), mouse MMR (Mrc1) sense (5'-CTCGTGGATCTCCGTGACAC-3'), mouse MMR (Mrc1) antisense (5'-GCAAATGGAGCCGTCTGTGC-3'), mouse arginase 1 sense (5'-ATGGAAGAGACCTTCAGCTAC-3'), mouse arginase 1 antisense (5'-GCTGTCTTCCCAAGAGTTGGG-3'), human ribosomal protein S12 sense (5'-GAATTCGCGAAGCTGCCAAA-3'), human ribosomal protein S12 antisense (5'-GACTCCTTGCCATAGTCCTT-3'), hMGL sense (5'-CCTCAGTGACCCTGAAGGA -3'), hMGL antisense (5'-AAAGGCAGCTCAGTGACTCT-3'), human MMR (Mrc1) sense (5'-CCTCTGGTGAACGGAATGAT-3'), human MMR (Mrc1) antisense (5'-AGGCCAGCACCCGTTAAAAT-3'), human arginase 1 sense (5'-GGCAAGGTGATGGAAGAAAC-3'), and human arginase 1 antisense (5'-AGTCCGAAACAAGCCAAGGT-3'). For all these primers, each PCR cycle consisted of 1 min denaturation at 94°C, 45 s annealing at 55°C, and 1 min extension at 72°C. Gene expression was normalized using ribosomal protein S12 as a housekeeping gene. Similar results were obtained using other housekeeping genes.
Detection of surface-antigen expression in flow cytometry
Total cells from peritoneal lavage (PEC) were incubated with appropriately diluted PE-bound anti-F4/80 antibodies (Serotec) and FITC-conjugated ER-MP23 anti-MGL antibodies (P. J. M. Leenen, Erasmus Medical Centre, Rotterdam, The Netherlands) or FITC-conjugated, isotype-matched, control antibodies (BD PharMingen) at 4°C for 30 min. Positive cells were determined with a FACSVantage station (BD Biosciences), and data were analyzed with CellQuest software.
Statistical analysis
All comparisons were tested for statistical significance (P<0.05) via the unpaired t-test using GraphPad Prism 3.0 software.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Expression analysis revealed that mMGL1 and mMGL2, similar to the previously known aaMF markers arginase 1, MMR, FIZZ1, and Ym, were significantly induced in peritoneal macrophages from chronic stage trypanosome-infected mice (aaMF) as compared with macrophages from early stage-infected (caMF) or noninfected mice (Fig. 1A ). It should hereby be remarked that expression of Ym, used as one of the reference markers for aaMF, was analyzed using "consensus" primers amplifying Ym1 and Ym2.
|
mMGL1 and mMGL2 as markers for allergy-induced aaMF
To examine whether the enhanced expression of mMGL1 and mMGL2 in aaMF occurs in other macrophage populations besides peritoneal macrophages and in other disease models besides parasite infections, allergic, type II, cytokine-dependent, pulmonary inflammation was induced in sensitized mice by exposure to OVA aerosols, and gene expression was monitored in alveolar macrophages. mMGL1 and mMGL2 were clearly induced in these alveolar aaMF, as compared with alveolar macrophages from control animals (Fig. 1C)
. Similar results were obtained for arginase 1 and FIZZ1. It is interesting that for Ym and MMR, the fold of induction in alveolar macrophages from OVA-challenged as compared with nonchallenged, control mice was rather low or not significant, respectively (Fig. 1C)
. However, it should be emphasized that alveolar macrophages from control animals constitutively express at least 5000-fold higher levels of Ym and MMR as compared with control peritoneal macrophages. In contrast, the basal expression of arginase 1, FIZZ1, mMGL1, and mMGL2 in alveolar and peritoneal macrophages was comparable or lower in alveolar macrophages than in peritoneal macrophages (data not shown).
In vitro cytokine modulation and in vivo dependence on cytokine signaling of mMGL1 and mMGL2 expression
To verify the association of mMGL1 and mMGL2 with type II, cytokine-induced aaMF, thioglycollate-elicited peritoneal macrophages were incubated with the type I cytokine IFN- or the type II cytokines IL-4 or IL-13, where IL-4 and IL-13, but not IFN-, moderately induced mMGL1 expression and strongly induced mMGL2 expression (Fig. 2A
; data not shown for IL-13). A similar behavior was observed for the previously identified aaMF markers, arginase 1, MMR, FIZZ1, and Ym.
|
-deficient (IL-4R KO) BALB/c mice. In peritoneal macrophages from noninfected animals, no significant differences were detected in the expression levels of arginase 1, MMR, FIZZ1, Ym, mMGL1, or mMGL2 among the three types of mice. Also, upon T. crassiceps infection of the three types of mice, a similar parasite burden was recorded up to the time when peritoneal macrophages were isolated. Yet, induction of mMGL1 and mMGL2, similar to arginase 1 and FIZZ1, was marginal or not significant in IL-4 KO as compared with WT mice during infection (Fig. 2B)
. Although the in vivo induction of Ym and MMR was also reduced drastically in the absence of IL-4, a significant induction of these two genes was still recorded in infected IL-4 KO mice. This residual induction of MMR and Ym may be a result of IL-13 signaling, as their fold of induction was further reduced in IL-4R KO mice, lacking IL-4 and IL-13 signaling [18
]. Hence, in this infection model, expression of this set of aaMF markers, including the novel mMGL1 and mMGL2 markers, requires IL-4R-mediated signaling. This is in accordance with what has been documented before for arginase 1 [19
] and MMR [20
] during Schistosoma mansoni infection and for FIZZ1 and Ym during trypanosome infections [6
].
Surface expression of MGL on aaMF
After having established that mMGL1 and mMGL2 mRNAs are induced in alternatively but not caMF, in vivo and in vitro, we next assessed if the induction of mMGL mRNA is reflected at the protein level and hence, whether this lectin would represent a useful surface marker for aaMF. To this aim, expression of mMGL was tested on aaMF, using the ER-MP23 monoclonal antibody, which recognizes an epitope on mouse MGL [21
22
23
]. As far as the specificity of this antibody is concerned, the N-terminal sequence (first 7 amino acids) of a protein precipitated with ER-MP23 was found to match the published sequence of mMGL1. In addition, ER-MP23 was shown to bind rmMGL1 in enzyme-linked immunosorbent assay (P. J. M. Leenen, unpublished observations). Yet, in view of the high sequence homology between mMGL1 and mMGL2 [17
], it cannot be excluded that this antibody also binds mMGL2. As shown in Figure 3
, peritoneal macrophages from T. crassiceps-infected mice exhibited increased surface expression of MGL as compared with a low basal expression in peritoneal macrophages from noninfected mice.
|
, expression of certain genes with AMAC-1 as the most promising example was found to be associated with alternative activation of human macrophages [16
]. Yet, no murine homologue of AMAC-1, acting as a marker for aaMF, has currently been defined.
To analyze if hMGL, for which, so far, only one single gene locus has been identified [25
], might represent a marker for human aaMF, human peripheral blood monocytes were treated in vitro with IL-4 or IFN-. Similar to hMMR and AMAC-1 but unlike human arginase 1, hMGL expression in monocytes was significantly induced by IL-4 but not by IFN- (Fig. 4
).
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Also, in human peripheral blood monocytes, MGL and MMR but not arginase 1 acted as markers for IL-4-elicited aaMF.
Overall, the results presented in this paper indicate that these markers should provide a toolbox to analyze the dynamic changes that are occurring in macrophage populations and the role of the various types of activated macrophages as well as the associated gene products in a wide range of physiological and pathological situations.
Functionally, murine MGL was documented to be involved in the receptor-mediated uptake of galactosylated glycoproteins and to act as a recognition molecule for glycosylated antigens on cancer cells [26
, 27
]. Upon molecular cloning of mMGL2, it was demonstrated that mMGL1 and mMGL2 have distinct carbohydrate specificities, and mMGL1 binds preferentially to Lewis X moieties, whereas mMGL2 has specificity for -N-acetylgalactosamine (-GalNAc) and ß-GalNAc residues [17
]. Transfection of a cell line with mMGL1 and adoptive transfer in tumor-bearing mice was shown to result in a preferential accumulation of these cells in lung metastatic nodules [28
], suggesting a role of MGL in homing of (tumoricidal) macrophages. Human MGL, exhibiting 60% amino acid identity to mMGL1 within the carbohydrate recognition domain, was shown to have carbohydrate-binding capacity for galactose and GalNAc and to recognize Tn antigen, a carcinoma-associated epitope, consisting of a cluster of serine or threonine-linked GalNAc [29
].
As far as expression is concerned, murine MGL was originally documented to have a strong association with macrophages residing in connective tissues or infiltrating in metastatic nodules of tumor-bearing mice [30 ]. Recent studies demonstrated that immature dendritic cells express human and murine MGL, where they are involved in the uptake of glycosylated antigens [25 , 31 ]. This paper is the first report documenting an association of MGL with alternative activation of macrophages. The fact that we have found mMGL to be induced in aaMF but not caMF in various in vitro and in vivo settings strongly suggests that expression of mMGL on macrophages may be indicative if not truly specific for aaMF. These results link the initial observations of mMGL expression on tumor-infiltrating macrophages [30 ], with the current paradigm that tumor-associated macrophages are polarized aaMF [32 ]. Expression of mMGL on connective tissue macrophages [23 , 30 ] points to the intriguing possibility that these macrophages may be activated alternatively.
Along with MMR, the prototype marker for type II, cytokine-dependent aaMF [3 ] and Ym [33 ], mMGL1, and mMGL2 form yet another set of lectins associated with aaMF. Moreover, expression of dectin-1, the major macrophage receptor for ß-glucans, was recently documented to be highly up-regulated by IL-4 and IL-13 [34 ]. It is tempting to speculate that these lectins, next to being pattern recognition molecules involved in the effector function and/or homing of aaMF, may also recognize immunomodulatory glycosylated compounds such as those identified from helminths [35 ] and may, hence, contribute to modulation of the macrophage activation state and, as such, to immune modulation. Indeed, whereas the role of Toll-like receptors in the generation of type I immune responses upon recognition of microbial stimuli has been firmly established [36 ], to date, there is little information concerning receptors and pathways involved in the generation of type II immune responses. In this context, MMR was recently documented to bind to S. mansoni egg antigens [20 ], and carbohydrate components from such egg antigens were shown to exert potent immunomodulatory properties [37 ]. It is intriguing that among the S. mansoni egg-derived glycan structures, lacto-N-fucopentaose III, which contains the Lewis X trisaccharide, was shown to exert adjuvant activity for the induction of type II immune responses [38 ]. Hence, it will be interesting to evaluate the contribution of mMGL1, which binds to Lewis X-type carbohydrates [17 ], in the induction of type II immune responses by these types of carbohydrates.
|
ACKNOWLEDGEMENTS |
|---|
Received March 31, 2004; revised November 12, 2004; accepted November 15, 2004.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
-deficient mice in chronic leishmaniasis reveal a protective role for IL-13 receptor signaling J. Immunol. 162,7302-7308 with a Th2-associated expression pattern J. Immunol. 160,1411-1418This article has been cited by other articles:
|
|
 |
|
  A. C. MacKinnon, S. L. Farnworth, P. S. Hodkinson, N. C. Henderson, K. M. Atkinson, H. Leffler, U. J. Nilsson, C. Haslett, S. J. Forbes, and T. Sethi Regulation of Alternative Macrophage Activation by Galectin-3 J. Immunol., February 15, 2008; 180(4): 2650 - 2658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Raymond, M. Schaller, C. M. Hogaboam, N. W. Lukacs, R. Rochford, and S. L. Kunkel Toll-like Receptors, Notch Ligands, and Cytokines Drive the Chronicity of Lung Inflammation Proceedings of the ATS, December 1, 2007; 4(8): 635 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Stijlemans, T. N. Baral, M. Guilliams, L. Brys, J. Korf, M. Drennan, J. Van Den Abbeele, P. De Baetselier, and S. Magez A Glycosylphosphatidylinositol-Based Treatment Alleviates Trypanosomiasis-Associated Immunopathology J. Immunol., September 15, 2007; 179(6): 4003 - 4014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mishra, M. Wang, J. Schlotman, N. M. Nikolaidis, C. W. DeBrosse, M. L. Karow, and M. E. Rothenberg Resistin-like molecule-beta is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L305 - L313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Sano, K. Usami, R. Izawa, K. Denda-Nagai, N. Higashi, T. Kimura, N. Suzuki, and T. Irimura Properties of Blocking and Non-blocking Monoclonal Antibodies Specific for Human Macrophage Galactose-type C-type Lectin (MGL/ClecSF10A/CD301) J. Biochem., January 1, 2007; 141(1): 127 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Devoogdt, H. Revets, A. Kindt, Y. Q. Liu, P. De Baetselier, and G. H. Ghassabeh The Tumor-Promoting Effect of TNF-{alpha} Involves the Induction of Secretory Leukocyte Protease Inhibitor J. Immunol., December 1, 2006; 177(11): 8046 - 8052. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Caljon, J. Van Den Abbeele, B. Stijlemans, M. Coosemans, P. De Baetselier, and S. Magez Tsetse Fly Saliva Accelerates the Onset of Trypanosoma brucei Infection in a Mouse Model Associated with a Reduced Host Inflammatory Response Infect. Immun., November 1, 2006; 74(11): 6324 - 6330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dupasquier, P. Stoitzner, H. Wan, D. Cerqueira, A. van Oudenaren, J. S. A. Voerman, K. Denda-Nagai, T. Irimura, G. Raes, N. Romani, et al. The dermal microenvironment induces the expression of the alternative activation marker CD301/mMGL in mononuclear phagocytes, independent of IL-4/IL-13 signaling J. Leukoc. Biol., October 1, 2006; 80(4): 838 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Reece, M. C. Siracusa, and A. L. Scott Innate Immune Responses to Lung-Stage Helminth Infection Induce Alternatively Activated Alveolar Macrophages Infect. Immun., September 1, 2006; 74(9): 4970 - 4981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wang, M. Campo, L. Ting, C. Fleming, C. Terhorst, and P. W. Finn The Costimulatory Molecule SLAM Is Critical for Pulmonary Allergic Responses Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 206 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Van Ginderachter, S. Meerschaut, Y. Liu, L. Brys, K. De Groeve, G. Hassanzadeh Ghassabeh, G. Raes, and P. De Baetselier Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer Blood, July 15, 2006; 108(2): 525 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Hassanzadeh Ghassabeh, P. De Baetselier, L. Brys, W. Noel, J. A. Van Ginderachter, S. Meerschaut, A. Beschin, F. Brombacher, and G. Raes Identification of a common gene signature for type II cytokine-associated myeloid cells elicited in vivo in different pathologic conditions Blood, July 15, 2006; 108(2): 575 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Joerink, C. M. S. Ribeiro, R. J. M. Stet, T. Hermsen, H. F. J. Savelkoul, and G. F. Wiegertjes Head Kidney-Derived Macrophages of Common Carp (Cyprinus carpio L.) Show Plasticity and Functional Polarization upon Differential Stimulation J. Immunol., July 1, 2006; 177(1): 61 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Erdely, D. Kepka-Lenhart, M. Clark, P. Zeidler-Erdely, M. Poljakovic, W. J. Calhoun, and S. M. Morris Jr Inhibition of phosphodiesterase 4 amplifies cytokine-dependent induction of arginase in macrophages Am J Physiol Lung Cell Mol Physiol, March 1, 2006; 290(3): L534 - L539. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Biswas, L. Gangi, S. Paul, T. Schioppa, A. Saccani, M. Sironi, B. Bottazzi, A. Doni, B. Vincenzo, F. Pasqualini, et al. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-{kappa}B and enhanced IRF-3/STAT1 activation) Blood, March 1, 2006; 107(5): 2112 - 2122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Raes, R. Van den Bergh, P. De Baetselier, G. H. Ghassabeh, C. Scotton, M. Locati, A. Mantovani, and S. Sozzani Arginase-1 and Ym1 Are Markers for Murine, but Not Human, Alternatively Activated Myeloid Cells J. Immunol., June 1, 2005; 174(11): 6561 - 6562. [Full Text] [PDF]
|
|
|
|
|
|
L. Brys, A. Beschin, G. Raes, G. H. Ghassabeh, W. Noel, J. Brandt, F. Brombacher, and P. D. Baetselier Reactive Oxygen Species and 12/15-Lipoxygenase Contribute to the Antiproliferative Capacity of Alternatively Activated Myeloid Cells Elicited during Helminth Infection J. Immunol., May 15, 2005; 174(10): 6095 - 6104. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||
