HEPATOCYTE GROWTH-FACTOR AND MACROPHAGE INFLAMMATORY PROTEIN 1-BETA -STRUCTURALLY DISTINCT CYTOKINES THAT INDUCE RAPID CYTOSKELETAL CHANGES AND SUBSET-PREFERENTIAL MIGRATION IN T-CELLS

T-cell migration into tissue depends on a cascade of rapid and selecti ve 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 demo nstrate that HGF can induce both adhesion and migration of human T-cel l subsets and can be detected immunohistochemically on inflamed endoth elium. HGF preferentially induces responses from T cells of memory phe notype, in contrast to macrophage inflammatory protein 1 beta (MIP-1 b eta), a chemokine which acts preferentially on naive cells. HGF, like the chemokines, binds to heparin, and HGF retained in extracellular ma trix is efficient in promoting migration. Further, both MIP-1 beta and HGF induce actin polymerization within seconds, kinetics that approac h those required to contribute to physiologic triggering. HGF is a mem ber of a structural family distinct from the chemokines, whose only kn own receptor is the tyrosine kinase c-Met. HGF induces tyrosine phosph orylation on T cells apparently via a distinct receptor, since no c-Me t is detectable by surface staining, PCR, or anti-phosphotyrosine immu noprecipitation. Thus, promotion of T-cell adhesion and migration are previously undescribed functions of HGF that we propose are relevant t o selective T-cell recruitment.