RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis.
RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis.
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DOI：
10.1084/jem.185.7.1371
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发表时间：
1997-04-07
期刊：
影响因子：
--
通讯作者：
Gutierrez-Ramos JC
中科院分区：
文献类型：
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作者：
Lloyd CM;Minto AW;Dorf ME;Proudfoot A;Wells TN;Salant DJ;Gutierrez-Ramos JC
趋化因子在炎症中的参与是公认的，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，还不清楚。为了研究趋化因子单核细胞趋化蛋白-1（MCP-1）和RANTES在新月体肾炎炎症和纤维化进展中的功能作用，我们开发了一种该综合征的小鼠模型并进行了表征。在疾病开始后早期，通过诱导MCP-1和RANTES的mRNA表达，在肾小球和肾小球内观察到T淋巴细胞和巨噬细胞的显著增加。阻断MCP-1或RANTES的功能导致蛋白尿以及浸润白细胞数量的显著减少，表明MCP-1和RANTES（在表达和分泌的正常T细胞活化后调节）在新月体肾炎的炎症阶段中起重要作用。此外，MCP-1的中和导致肾小球新月体形成和I型胶原沉积的急剧减少。这些结果突出了MCP-1在新月体形成和间质纤维化发展中的新作用，并表明除了招募炎性细胞外，这种趋化因子还与不可逆的组织损伤密切相关。
The involvement of chemokines in inflammation is well established, but their functional role in disease progression, and particularly in the development of fibrosis, is not yet understood. To investigate the functional role that the chemokines monocyte chemoattractant protein–1 (MCP-1) and RANTES play in inflammation and the progression to fibrosis during crescentic nephritis we have developed and characterized a murine model for this syndrome. Significant increases in T-lymphocytes and macrophages were observed within glomeruli and interstitium, paralleled by an induction of mRNA expression of MCP-1 and RANTES, early after disease initiation. Blocking the function of MCP-1 or RANTES resulted in significant decreases in proteinuria as well as in numbers of infiltrating leukocytes, indicating that both MCP-1 and RANTES (regulated upon activation in normal T cells expressed and secreted) play an important role in the inflammatory phase of crescentic nephritis. In addition, neutralization of MCP-1 resulted in a dramatic decrease in both 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.