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
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DOI：
10.1046/j.1523-1755.1999.00646.x
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发表时间：
1999-09-01
影响因子：
19.6
通讯作者：
Yokoyama, H
中科院分区：
文献类型：
--
作者：
Wada, T;Furuichi, K;Yokoyama, H
背景巨噬细胞（M phi）的招募和激活在新月体肾炎的确切分子机制仍有待研究。我们假设局部产生的巨噬细胞炎性蛋白（MIP）-1 α和单核细胞趋化蛋白（MCP）-1通过趋化因子受体参与人新月体肾小球肾炎的病理生理学，通过募集和激活M φ。我们通过酶联免疫吸附试验（ELISA）检测了20例健康受试者、20例新月体肾炎患者和41例其他各种肾脏疾病对照患者的MIP-1 α和MCP-1水平。通过免疫组化和原位杂交分析评估MIP-1 α、MCP-1和MIP-1 α的同源趋化因子受体CCR 5在病变肾脏中的存在。MIP-1 α阳性细胞主要在新月体病变中检测到，而MCP-1主要在肾小球中。此外，我们还在病变肾小球和肾小球中检测到CCR 5阳性细胞。尿MIP-1 α在新月体肾小球肾炎中被检测到，即使它低于健康受试者和无新月体的其他肾脏疾病患者的可检测水平。新月体肾炎患者尿MIP-1 α水平与肾小球中新月体细胞百分比、CD 68阳性浸润细胞和CCR 5阳性细胞数量密切相关。但尿MCP-1水平与新月体总数、纤维细胞/纤维新月体的百分比以及肾小球中CD 68阳性浸润细胞的数量密切相关。这些观察结果表明，局部产生的MIP-1 α可能通过CCR 5参与急性期细胞新月体的发展，MCP-1可能主要参与慢性期纤维细胞/纤维新月体存在时间质病变的发展，可能通过M phi募集和激活。
Background. The precise molecular mechanisms of macrophage (M phi) recruitment and activation in crescentic glomerulonephritis remain to be investigated. We hypothesized that locally produced macrophage inflammatory protein (MIP)-1 alpha and monocyte chemoattractant protein (MCP)-1 via the chemokine receptors participate in the pathophysiology of human crescentic glomerulonephritis by recruiting and activating M phi.Methods. We investigated the levels of MIP-1 alpha 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-1 alpha, MCP-1, and the cognate chemokine receptor for MIP-1 alpha, CCR5, in the diseased kidneys was evaluated by immunohistochemical and in situ hybridization analyses.Results. MIP-1 alpha-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-1 alpha 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-1 alpha 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-1 alpha and MCP-1 dramatically decreased during glucocorticoid therapy-induced convalescence.Conclusions. These observations suggest that locally produced MIP-1 alpha 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 M phi recruitment and activation.