title: Distinct tissue site-specific requirements of mast cells and complement components C3/C5a receptor in IgG immune complex-induced injury of skin and lung.
abstract: We induced the passive reverse Arthus reaction to IgG immune complexes (IC) at different tissue sites in mice lacking C3 treated or not with a C5aR-specific antagonist, or in mice lacking mast cells (Kit(W)/Kit(W-v) mice), and compared the inflammatory responses with those in the corresponding wild-type mice. We confirmed that IC inflammation of skin can be mediated largely by mast cells expressing C5aR and FcgammaRIII. In addition, we provided evidence for C3-independent C5aR triggering, which may explain why the cutaneous Arthus reaction develops normally in C3(-/-) mice. Furthermore, some, but not all, of the acute changes associated with the Arthus response in the lung were significantly more intense in normal mice than in C3(-/-) or Kit(W)/Kit(W-v) mice, indicating for C3- and mast cell-dependent and -independent components. Finally, we demonstrated that C3 contributed to the elicitation of neutrophils to alveoli, which corresponded to an increased synthesis of TNF-alpha, macrophage-inflammatory protein-2, and cytokine-induced neutrophil chemoattractant. While mast cells similarly influenced alveolar polymorphonuclear leukocyte influx, the levels of these cytokines remained largely unaffected in mast cell deficiency. Together, the phenotypes of C3(-/-) mice and Kit(W)/Kit(W-v) mice suggest that complement and mast cells have distinct tissue site-specific requirements acting by apparently distinct mechanisms in the initiation of IC inflammation.
authors: Department of Clinical Immunology, Medical School Hannover, 30625 Hannover, Germany.
authors: U
authors: U
authors: Baumann
authors: N
authors: N
authors: Chouchakova
authors: B
authors: B
authors: Gewecke
authors: J
authors: J
authors: Köhl
authors: M C
authors: MC
authors: Carroll
authors: R E
authors: RE
authors: Schmidt
authors: J E
authors: JE
authors: Gessner
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D001183:Arthus Reaction / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015936:Complement C5a / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D007105:Immune Complex Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007074:Immunoglobulin G / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000502:physiology*; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; D003176:Complement C3; D016207:Cytokines; D007074:Immunoglobulin G; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D015936:Complement C5a