MIP-1α and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis

MIP-1α and MCP-1 contribute to crescents and interstitial lesions in human crescentic glomerulonephritis.BackgroundThe precise molecular mechanisms of macrophage (Mϕ) recruitment and activation in crescentic glomerulonephritis remain to be investigated. We hypothesized that locally produced macrophage inflammatory protein (MIP)-1α and monocyte chemoattractant protein (MCP)-1 via the chemokine receptors participate in the pathophysiology of human crescentic glomerulonephritis by recruiting and activating Mϕ.MethodsWe investigated the levels of MIP-1α and MCP-1 by enzyme-linked immunosorbent assay (ELISA) in 20 healthy subjects, 20 patients with crescentic glomerulonephritis, and 41 control patients with various other renal diseases. The presence of MIP-1α, MCP-1, and the cognate chemokine receptor for MIP-1α, CCR5, in the diseased kidneys was evaluated by immunohistochemical and in situ hybridization analyses.ResultsMIP-1α–positive cells were mainly detected in crescentic lesions, whereas MCP-1 was mainly in the interstitium. In addition, we detected CCR5-positive cells in diseased glomeruli and interstitium. Urinary MIP-1α was detected in crescentic glomerulonephritis, even though it was below detectable levels in healthy subjects and in patients with other renal diseases without crescents. Urinary MIP-1α levels in the patients with crescentic glomerulonephritis were well correlated with the percentage of cellular crescents and the number of CD68-positive infiltrating cells and CCR5-positive cells in the glomeruli. However, urinary MCP-1 levels were well correlated with the percentage of both total crescents and fibrocellular/fibrous crescents and the number of CD68-positive infiltrating cells in the interstitium. Moreover, elevated urinary levels of both MIP-1α and MCP-1 dramatically decreased during glucocorticoid therapy-induced convalescence.ConclusionsThese observations suggest that locally produced MIP-1α may be involved in the development of cellular crescents in the acute phase via CCR5 and that MCP-1 may be involved mainly in the development of interstitial lesions in the chronic phase when fibrocellular/fibrous crescents are present, possibly through Mϕ recruitment and activation