Role of MCP-1 and RANTES in inflammation and progression to fibrosis during murine crescentic nephritis
Role of MCP-1 and RANTES in inflammation and progression to fibrosis during murine crescentic nephritis
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DOI：
10.1002/jlb.62.5.676
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发表时间：
1997-11-01
影响因子：
5.5
通讯作者：
GutierrezRamos, JC
中科院分区：
文献类型：
--
作者：
Lloyd, CM;Dorf, ME;GutierrezRamos, JC
趋化因子炎症的参与已经得到了很好的证实，但它们在疾病进展中的功能作用，特别是在纤维化的发展中，尚不清楚。我们研究了趋化因子单核细胞趋化蛋白-1 （MCP-1）和RANTES在月牙状肾炎期间炎症和纤维化进展中的功能作用。在这种疾病中，肾小球和间质内可见炎症浸润，MCP-1和RANTES表达增加，肾功能下降。疾病进展的标志是肾小球月牙形的形成和I型胶原的沉积，阻断MCP-1或RANTES的功能导致蛋白尿和浸润性白细胞数量的显著减少，表明MCP-1和RANTES在月牙形肾炎的炎症期起重要作用，特别是MCP-1的中和作用，而RANTES不起作用。导致肾小球新月形成和I型胶原沉积的急剧减少。这些结果强调了MCP-1在新月形成和间质纤维化发展中的新作用，并表明除了募集炎症细胞外，这种趋化因子还严重参与不可逆组织损伤。
The involvement of chemokines inflammation is well established but their functional role in disease progression, and particularly in the development of fibrosis, is not yet understood, We have investigated the functional role that the chemokines monocyte chemotactic protein-1 (MCP-1) and RANTES play in inflammation and the progression to fibrosis during crescentic nephritis, During this disease inflammatory infiltrates are observed within glomeruli and interstitium in conjunction with increased expression of MCP-1 and RANTES and a decrease in renal function. Disease progression is marked by formation of glomerular crescents and the deposition of type I collagen, Blocking the function of MCP-1 or RANTES resulted in significant decreases in proteinuria as well as numbers of infiltrating leukocytes, indicating that both MCP-1 and RANTES play an important role in the inflammatory phase of crescentic nephritis, In particular, neutralization of MCP-1, but not RANTES, resulted in a dramatic decrease in glomerular crescent formation and deposition of type I collagen. These results highlight a novel role for MCP-1 in crescent formation and development of interstitial fibrosis and indicate that in addition to recruiting inflammatory cells this chemokine is critically involved in irreversible tissue damage.