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. 1994 Jul 19;91(15):7144–7148. doi: 10.1073/pnas.91.15.7144

Hepatocyte growth factor and macrophage inflammatory protein 1 beta: structurally distinct cytokines that induce rapid cytoskeletal changes and subset-preferential migration in T cells.

D H Adams 1, L Harvath 1, D P Bottaro 1, R Interrante 1, G Catalano 1, Y Tanaka 1, A Strain 1, S G Hubscher 1, S Shaw 1
PMCID: PMC44355  PMID: 8041760

Abstract

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.

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