TY - JOUR
T1 - Mast cell-mediated remodeling and fibrinolytic activity protect against fatal glomerulonephritis
AU - Kanamaru, Yutaka
AU - Scandiuzzi, Lisa
AU - Essig, Marie
AU - Brochetta, Cristiana
AU - Guérin-Marchand, Claudine
AU - Tomino, Yasuhiko
AU - Monteiro, Renato C.
AU - Peuchmaur, Michel
AU - Blank, Ulrich
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2006/5/1
Y1 - 2006/5/1
N2 - 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 congenially mast cell-deficient W/WV 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/WV mice restored protection. This was independent of activating FcγR, as protection was also obtained using mast cells deficient in FcRγ. 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/WV mice, while +/+ mice or mast cell-reconstituted W/WV 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.
AB - 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 congenially mast cell-deficient W/WV 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/WV mice restored protection. This was independent of activating FcγR, as protection was also obtained using mast cells deficient in FcRγ. 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/WV mice, while +/+ mice or mast cell-reconstituted W/WV 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.
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U2 - 10.4049/jimmunol.176.9.5607
DO - 10.4049/jimmunol.176.9.5607
M3 - Article
C2 - 16622030
AN - SCOPUS:33645971613
SN - 0022-1767
VL - 176
SP - 5607
EP - 5615
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -