title: Mast cell-mediated remodeling and fibrinolytic activity protect against fatal glomerulonephritis.
abstract: Mast cells are detrimental in several inflammatory diseases; however, their physiological roles are also increasingly recognized. Recent data suggest that mast cells may also be involved in renal diseases. We therefore used congenitally mast cell-deficient W/W(v) mice and normal +/+ littermates to assess their role in anti-glomerular basement membrane-induced glomerulonephritis. Following administration of anti-glomerular basement membrane Abs, W/W(v) mice exhibited increased mortality as compared with +/+ mice owing to rapid deterioration of renal function. Reconstitution of the mast cell population in W/W(v) mice restored protection. This was independent of activating FcgammaR, as protection was also obtained using mast cells deficient in FcRgamma. Comparative histological analysis of kidneys showed that deterioration of renal function was caused by the presence of thick layers of subendothelial glomerular deposits in W/W(v) mice, while +/+ mice or mast cell-reconstituted W/W(v) mice showed significantly less. Deposits appeared during the early phase of disease and persisted thereafter, and were accompanied by enhanced macrophage recruitment. Immunohistochemical analysis revealed increased amounts of fibrin and type I collagen in W/W(v) mice, which were also unable to maintain high tissue plasminogen activator and urinary-type plasminogen activator activity in urine in the heterologous phase of disease. Our results indicate that mast cells by their ability to mediate remodeling and repair functions are protective in immune complex-mediated glomerulonephritis.
authors.affiliation: INSERM Unité 699, Faculté de Médecine X, Bichat Medical School, 16 rue Henri Huchard, 75780 Paris Cedex 18, France.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kanamaru
authors.forename: Lisa
authors.initials: L
authors.lastname: Scandiuzzi
authors.forename: Marie
authors.initials: M
authors.lastname: Essig
authors.forename: Cristiana
authors.initials: C
authors.lastname: Brochetta
authors.forename: Claudine
authors.initials: C
authors.lastname: Guérin-Marchand
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
authors.forename: Michel
authors.initials: M
authors.lastname: Peuchmaur
authors.forename: Ulrich
authors.initials: U
authors.lastname: Blank
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D006224:Cricetinae; D004198:Disease Susceptibility; D042783:Endothelial Cells / Q000166:cytology; D005337:Fibrin / Q000378:metabolism; D050533:Glomerular Basement Membrane / Q000276:immunology; D005921:Glomerulonephritis / Q000196:embryology / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages; D008407:Mast Cells; D051379:Mice; D017452:Receptors, IgG / Q000378:metabolism; D015996:Survival Rate
chemical_list: D000906:Antibodies; D017452:Receptors, IgG; D005337:Fibrin; D003094:Collagen