Impaired inflammatory responses in the reverse arthus reaction through genetic deletion of the C5a receptor.
We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex-mediated inflammation. In this study, we compare the effect of C5aR deficiency in immune complex-induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model. C5aR- deficient mice exhibit decreased migration of neutrophils and decreased levels of TNF-alpha and interleukin 6 in the peritoneal reverse passive Arthus reaction compared to their wild-type littermates. In the reverse passive Arthus reaction in the skin the C5aR was also required for the full expression of neutrophil influx and edema formation; C5aR-deficient mice showed reduced neutrophil migration and microvascular permeability changes. In contrast to our studies in immune complex-induced lung inflammation, C5aR deficiency does not completely prevent injury in the peritoneal cavity and skin. These data indicate a dominant role for the C5aR and its ligand in the reverse passive Arthus reaction in the lung and a synergistic role together with other inflammatory mediators in immune complex-mediated peritonitis and skin injury.
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Ina Sue Perlmutter Cystic Fibrosis Laboratory, Children's Hospital, Department of Medicine, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
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D000818:Animals; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001183:Arthus Reaction / Q000276:immunology*; D002199:Capillary Permeability; D002452:Cell Count; D003165:Complement System Proteins / Q000276:immunology; D004487:Edema / Q000276:immunology; D018390:Gene Targeting; D007105:Immune Complex Diseases / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000032:analysis; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010538:Peritonitis / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011961:Receptors, Fc / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000906:Antibodies; D015703:Antigens, CD; D007074:Immunoglobulin G; D015850:Interleukin-6; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D010047:Ovalbumin; D003165:Complement System Proteins; D009195:Peroxidase