Vimentin is secreted by activated macrophages
Vimentin is secreted by activated macrophages
复制标题
DOI：
10.1038/ncb898
复制
发表时间：
2003-01-01
影响因子：
21.3
通讯作者：
Markovitz, DM
中科院分区：
文献类型：
--
作者：
Mor-Vaknin, N;Punturieri, A;Markovitz, DM
波形蛋白是一种广泛表达的中间丝蛋白，被认为主要参与结构过程，如伤口愈合（1）。我们现在证明，激活的人巨噬细胞分泌波形蛋白到细胞外空间。血液来源的单核细胞成熟为巨噬细胞涉及几种信号传导途径（2，3）。我们发现，分泌的波形蛋白，这是磷酸化的丝氨酸和苏氨酸残基，增强了磷酸酶抑制剂冈田酸和特定的蛋白激酶C抑制剂GO 6983阻断。这些发现与之前的观察结果一致，即波形蛋白的磷酸化影响其细胞内定位，波形蛋白是蛋白激酶C（PKC）的底物（4，5）。我们还表明，抗炎细胞因子白细胞介素-10（IL-10），抑制PKC活性，阻断波形蛋白的分泌。相反，促炎细胞因子肿瘤坏死因子α（TNF-α）可以触发波形蛋白的分泌。最后，我们发现细胞外波形蛋白参与细菌杀伤和氧化代谢产物的产生，这是活化的巨噬细胞的两个重要功能。这些数据表明，波形蛋白是由巨噬细胞分泌的，以响应促炎信号通路，并可能参与免疫功能。
Vimentin is a widely expressed intermediate filament protein thought to be involved mainly in structural processes, such as wound healing(1). We now demonstrate that activated human macrophages secrete vimentin into the extracellular space. The maturation of blood-derived monocytes into macrophages involves several signalling pathways(2,3). We show that secretion of vimentin, which is phosphorylated at serine and threonine residues, is enhanced by the phosphatase inhibitor okadaic acid and blocked by the specific protein kinase C inhibitor GO6983. These findings are consistent with previous observations that phosphorylation of vimentin affects its intracellular localization and that vimentin is a substrate for protein kinase C (PKC)(4,5). We also show that the anti-inflammatory cytokine interleukin-10 (IL-10), which inhibits PKC activity, blocks secretion of vimentin. In contrast, the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-alpha) can trigger secretion of vimentin. Finally, we found that extracellular vimentin is involved in bacterial killing and the generation of oxidative metabolites, two important functions of activated macrophages. These data establish that vimentin is secreted by macrophages in response to pro-inflammatory signalling pathways and is probably involved in immune function.