Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis
Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis
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DOI：
10.1172/jci200420997
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发表时间：
2004-08-01
影响因子：
15.9
通讯作者：
Strieter, RM
中科院分区：
文献类型：
--
作者：
Phillips, RJ;Burdick, MD;Strieter, RM
以前的报道已经鉴定了一个循环库的CD45（+）胶原I+ CXCR4（+）（CD45（+）Col I（+）CXCR4（+））细胞，称为纤维细胞，其运输到纤维化区域。然而，没有研究表明这些细胞实际上有助于纤维化。肺纤维化最初被认为仅由肺成纤维细胞介导。在此，我们发现在博莱霉素诱导的肺纤维化小鼠模型中，人CD 45（+）Col I（+）CXCR 4（+）循环纤维细胞群响应CXCL 12迁移并运输至肺。接下来，我们证明了鼠CD45（+）Col I（+）CXCR4（+）纤维细胞也响应博来霉素攻击而运输到肺。肺内CD 45（+）Col I（+）CXCR 4（+）纤维细胞的最大募集与肺内胶原沉积增加直接相关。用特异性中和性抗CXCL12抗体治疗博莱霉素暴露的动物，可抑制肺内CD 45（+）Col I（+）CXCR4（+）循环纤维细胞的募集，并减轻肺纤维化。因此，我们的研究结果表明，我们相信第一次，循环纤维细胞有助于肺纤维化的发病机制。
Previous reports have identified a circulating pool of CD45(+) collagen I+ CXCR4(+) (CD45(+)Col I(+)CXCR4(+)) cells, termed fibrocytes, that traffic to areas of fibrosis. No studies have demonstrated that these cells actually contribute to fibrosis, however. Pulmonary fibrosis was originally thought to be mediated solely by resident lung fibroblasts. Here we show that a population of human CD45(+)Col I(+)CXCR4(+) circulating fibrocytes migrates in response to CXCL12 and traffics to the lungs in a murine model of bleomycin-induced pulmonary fibrosis. Next, we demonstrated that murine CD45(+)Col I(+)CXCR4(+) fibrocytes also traffic to the lungs in response to a bleomycin challenge. Maximal intrapulmonary recruitment of CD45(+)Col I(+)CXCR4(+) fibrocytes directly correlated with increased collagen deposition in the lungs. Treatment of bleomycin-exposed animals with specific neutralizing anti-CXCL12 Ab's inhibited intrapulmonary recruitment of CD45(+)Col I(+)CXCR4(+) circulating fibrocytes and attenuated lung fibrosis. Thus, our results demonstrate, we believe for the first time, that circulating fibrocytes contribute to the pathogenesis of pulmonary fibrosis.