title: Pre-existing glomerular immune complexes induce polymorphonuclear cell recruitment through an Fc receptor-dependent respiratory burst: potential role in the perpetuation of immune nephritis.
abstract: In immune complex (IC) diseases, FcR are essential molecules facilitating polymorphonuclear cell (PMN) recruitment and effector functions at the IC site. Although FcR-dependent initial tethering and FcR/integrin-dependent PMN accumulation were postulated, their underlying mechanisms remain unclear. We here addressed potential mechanisms involved in PMN recruitment in acute IC glomerulonephritis (nephrotoxic nephritis). Since some renal cells may be recruited from bone marrow (BM) lineages, reconstitution studies with BM chimeras and PMN transfer between wild-type (WT) and FcR-deficient mice (gamma(-/-)) were performed. Severe glomerular damage was induced in WT and W gamma chimeras (BM from WT to irradiated gamma(-/-)), while it was absent in gamma(-/-) and gamma W chimeras (gamma(-/-) BM to WT). Moreover, WT PMN transfer, but not gamma(-/-) PMN, reconstituted the disease in gamma(-/-), indicating that FcR on resident cells is not a prerequisite for PMN recruitment in this disease. Surprisingly, transferred WT PMN were recruited coincidentally with NF-kappa B activation and TNF-alpha overexpression even in glomeruli with preformed IC (nephrotoxic Ab administered 3 days previously), suggesting that PMN can initially be recruited via its own FcR without previous chemoattractant release. Furthermore, H(2)O(2) inhibition by catalase attenuated the acute WT PMN recruitment and the induction of NF-kappa B and TNF-alpha much more than integrin (CD18) blockade, indicating a role for the respiratory burst before integrin-dependent accumulation. In coculture experiments with IC-stimulated PMN and glomeruli, PMN caused acute glomerular TNF-alpha expression predominantly via FcR-mediated H(2)O(2) production. In conclusion, glomerular IC, even preformed, can cause PMN recruitment and injury through PMN FcR-mediated respiratory burst during initial PMN tethering to IC.
authors.affiliation: Renal and Vascular Research Laboratory, Fundación Jiménez Díaz, Autónoma University, Madrid, Spain.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Carmen
authors.initials: C
authors.lastname: Gómez-Guerrero
authors.forename: Isao
authors.initials: I
authors.lastname: Shirato
authors.forename: Oscar
authors.initials: O
authors.lastname: López-Franco
authors.forename: Julio
authors.initials: J
authors.lastname: Gallego-Delgado
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanjuán
authors.forename: Alberto
authors.initials: A
authors.lastname: Lázaro
authors.forename: Purificación
authors.initials: P
authors.lastname: Hernández-Vargas
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.forename: Chisei
authors.initials: C
authors.lastname: Ra
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
mesh_terms: D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000936:Antigen-Antibody Complex / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology; D002374:Catalase / Q000494:pharmacology; D005260:Female; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000096:biosynthesis; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D011828:Radiation Chimera / Q000276:immunology; D011961:Receptors, Fc / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000936:Antigen-Antibody Complex; D018836:Inflammation Mediators; D016328:NF-kappa B; D011961:Receptors, Fc; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D002374:Catalase