HEPATOCYTE GROWTH-FACTOR AND MACROPHAGE INFLAMMATORY PROTEIN 1-BETA - STRUCTURALLY DISTINCT CYTOKINES THAT INDUCE RAPID CYTOSKELETAL CHANGES AND SUBSET-PREFERENTIAL MIGRATION IN T-CELLS
HEPATOCYTE GROWTH-FACTOR AND MACROPHAGE INFLAMMATORY PROTEIN 1-BETA - STRUCTURALLY DISTINCT CYTOKINES THAT INDUCE RAPID CYTOSKELETAL CHANGES AND SUBSET-PREFERENTIAL MIGRATION IN T-CELLS
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DOI：
10.1073/pnas.91.15.7144
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发表时间：
1994-07-19
影响因子：
11.1
通讯作者：
SHAW, S
中科院分区：
文献类型：
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作者：
ADAMS, DH;HARVATH, L;SHAW, S
T细胞向组织中的迁移依赖于与内皮的快速和选择性粘附相互作用的级联。“触发”是激活T细胞整合素所需的级联反应中的一个步骤。肝细胞生长因子（HGF）可能是一个生理相关的触发器，因为我们证明，HGF可以诱导粘附和迁移的人T细胞亚群，并可以检测到炎症内皮细胞化学。与巨噬细胞炎性蛋白1 β（MIP-1 β）（一种优先作用于幼稚细胞的趋化因子）相反，HGF优先诱导来自记忆表型的T细胞的应答。与趋化因子一样，HGF与肝素结合，并且保留在细胞外基质中的HGF有效促进迁移。此外，MIP-1 β和HGF均在数秒内诱导肌动蛋白聚合，动力学接近有助于生理触发所需的动力学。HGF是不同于趋化因子的结构家族的成员，其唯一已知的受体是酪氨酸激酶c-Met。HGF诱导T细胞上的酪氨酸磷酸化显然是通过一个独特的受体，因为没有c-Met是可检测的表面染色，PCR，或抗磷酸酪氨酸免疫沉淀。因此，促进T细胞的粘附和迁移是以前未描述的功能，我们建议是相关的选择性T细胞招聘的HGF。
T-cell migration into tissue depends on a cascade of rapid and selective adhesive interactions with endothelium. ''Triggering'' is a step in that cascade required to activate T-cell integrins. Hepatocyte growth factor (HGF) may be a physiologically relevant trigger, since we demonstrate that HGF can induce both adhesion and migration of human T-cell subsets and can be detected immunohistochemically on inflamed endothelium. HGF preferentially induces responses from T cells of memory phenotype, in contrast to macrophage inflammatory protein 1 beta (MIP-1 beta), a chemokine which acts preferentially on naive cells. HGF, like the chemokines, binds to heparin, and HGF retained in extracellular matrix is efficient in promoting migration. Further, both MIP-1 beta and HGF induce actin polymerization within seconds, kinetics that approach those required to contribute to physiologic triggering. HGF is a member of a structural family distinct from the chemokines, whose only known receptor is the tyrosine kinase c-Met. HGF induces tyrosine phosphorylation on T cells apparently via a distinct receptor, since no c-Met is detectable by surface staining, PCR, or anti-phosphotyrosine immunoprecipitation. Thus, promotion of T-cell adhesion and migration are previously undescribed functions of HGF that we propose are relevant to selective T-cell recruitment.