A dominant role for Fc gamma receptors in antibody-dependent corneal inflammation.
Although production of specific Ab is a critical element of host defense, the presence of Ab in tissues leads to formation of immune complexes, which can trigger a type III Arthus reaction. Our studies on a mouse model of river blindness showed that Ab production is essential for recruitment of neutrophils and eosinophils to the cornea and for development of corneal opacification. In the current study, we determined the relative contribution of complement and FcgammaR interactions in triggering immune complex-mediated corneal disease. FcgammaR(-/-) mice, C3(-/-) mice, and immunocompetent control (B6/129Sj) mice were immunized s.c. and injected intrastromally with Onchocerca volvulus Ags. Slit lamp examination showed that control mice, C3(-/-) mice, and control mice injected with cobra venom factor developed pronounced corneal opacification, whereas corneas of FcgammaR(-/-) mice remained completely clear. Furthermore, recruitment of neutrophils and eosinophils to the corneal stroma was significantly impaired in FcgammaR(-/-) mice, but not in C3(-/-) mice or cobra venom factor-treated mice. We therefore conclude that FcgammaR-mediated cell activation, rather than complement activation, is the dominant pathway of immune complex disease in the cornea. These findings demonstrate a novel role for FcgammaR interactions in mediating ocular inflammation.
Hall
L R
LR
Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH 44106, USA.
Diaconu
E
E
Pearlman
E
E
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis / Q000502:physiology*; D000947:Antigens, Helminth / Q000276:immunology; D003176:Complement C3 / Q000172:deficiency / Q000235:genetics; D003319:Corneal Stroma / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000008:administration & dosage; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D007634:Keratitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000235:genetics; D017181:Onchocerca volvulus / Q000276:immunology; D015827:Onchocerciasis, Ocular / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017452:Receptors, IgG / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D003176:Complement C3; D004546:Elapid Venoms; D007132:Immunoglobulin Isotypes; D017452:Receptors, IgG; C016310:cobra venom factor