Matrix metalloproteinase-1 produced by human CXCL12-stimulated natural killer cells
Matrix metalloproteinase-1 produced by human CXCL12-stimulated natural killer cells
复制标题
DOI：
10.2353/ajpath.2006.050676
复制
发表时间：
2006-08-01
影响因子：
6
通讯作者：
Iida, Joji
中科院分区：
文献类型：
--
作者：
Goda, Seiji;Inoue, Hiroshi;Iida, Joji
自然杀伤细胞（NK）通过向组织迁移的能力在炎症和肿瘤消退中发挥关键作用。CXCL12是一种促进淋巴细胞侵袭和向组织迁移的趋化因子；然而，这一过程的机制仍然不完全清楚。在本研究中，我们发现CXCL12通过基质金属蛋白酶-1 （MMP-1）的催化活性显著增强CD16(+)CD56（+）人外周血nk细胞对I型胶原的侵袭。共聚焦免疫荧光和共免疫沉淀研究表明，MMP-1与α (2) β(1)整合素在cxcl -12刺激的nk细胞表面共定位。pro-MMP-1与α (2) β(1)整合素的结合需要激活G(i)偶联途径。然而，cxcl12刺激的NK细胞产生MMP-1是由p38和丝裂原激活或细胞外信号调节蛋白激酶激酶1/2介导的，其方式独立于G(i)偶联途径。这些结果表明，CXCL12/CXCR4相互作用通过两种信号通路促进nk细胞的侵袭，从而通过膜相关的MMP-1刺激细胞外基质蛋白的细胞周降解。因此，在生理和病理过程中，这种机制可能在促进淋巴细胞在组织中的运输和积累中发挥作用。
Natural killer (NK) cells play a key role in inflammation and tumor regression through their ability to migrate into tissues. CXCL12 is a chemokine that promotes lymphocyte invasion and migration into tissues; however, the mechanism for this process remains incompletely understood. in this study, we show that CXCL12 significantly enhanced CD16(+)CD56(+) human peripheral NK-cell invasion into type I collagen by the catalytic activity of matrix metalloproteinase-1 (MMP-1). Confocal immunofluorescence and co-immunoprecipitation studies suggest that MMP-1 colocalized with alpha(2)beta(1) integrin on CXCL-12-stimulated NK-cell surface. The binding of pro-MMP-1 with alpha(2)beta(1), integrin required activation of G(i)-coupled pathway. However, the production of MMP-1 from CXCL12-stimulated NK cells was mediated by p38 and mitogen-activated or extracellular signal-regulation protein kinase kinase 1/2 in a manner independent of the G(i)-coupled pathway. These results suggest that CXCL12/CXCR4 interaction transduces the two Signaling pathways to promote NK-cell invasion, which stimulates pericellular degradation of extracellular matrix proteins by membrane-associated MMP-1. The mechanisms would thus play a role in facilitating lymphocyte trafficking and accumulation in tissues during physiological and pathological processes.