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Intervention of crescentic glomerulonephritis by antibodies to monocyte chemotactic and activating factor (MCAF/MCP‐1)
Author(s) -
Wada Takashi,
Yokoyama Hitoshi,
Furuichi Kengo,
Kobayashi KenIchi,
Harada Kenji,
Naruto Masanobu,
Su ShaoBo,
Akiyama Mariko,
Mukaida Naofumi,
Matsushima Kouji
Publication year - 1996
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.10.12.8903512
Subject(s) - glomerulonephritis , monocyte , chemokine , medicine , chemotaxis , glomerulosclerosis , kidney , cytokine , antibody , ccl2 , proteinuria , immunology , endocrinology , inflammation , receptor
We investigated the pathophysiological role of a potent macrophage (Mϕ) chemotactic cytokine (chemokine), monocyte chemotactic and activating factor/monocyte chemoattractant protein‐1 (MCAF/MCP‐1), in an animal model of crescentic glomerulonephritis. Administration of a small dose of nephrotoxic sera induced severe proliferative and necrotizing glomerulonephritis, with crescentic formation in the early phase and glomerulosclerosis in the later phase, in Wistar‐Kyoto rats. MCAF/MCP‐1 protein was detected immunohistochemically in glomeruli, vascular endothelial cells, and tubular epithelial cells in the early phase of injured kidney tissues but not in normal ones. Anti‐MCAF/MCP‐1 antibodies decreased the number of Mϕ in glomeruli, and prevented crescentic formation and the fusion of epithelial cell foot process in nephritic rats, thereby decreasing the excreted amounts of protein to normal levels on days 3 and 6. Furthermore, anti‐MCAF/MCP‐1 antibodies remarkably reduced glomerulosclerosis and improved renal dysfunction as well as proteinuria in the later phase (56 days). These results indicate that MCAF/MCP‐1 essentially participates in the impairment of renal functions associated with crescentic glomerulonephritis by recruiting and activating Mϕ.—Wada, T., Yokoyama, H., Furuichi, K., Kobayashi, K.‐i., Harada, K., Naruto, M., Su, S.‐B., Akiyama, M., Mukaida, N., Matsushima, K. Intervention of crescentic glomerulonephritis by antibodies to monocyte chemotactic and activating factor (MCAF/MCP‐1). FASEB J. 10, 1418‐1425 (1996)