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

Research output: Contribution to journalArticle

Authors

  • D H Adams
  • L Harvath
  • D P Bottaro
  • R Interrante
  • G Catalano
  • Y Tanaka
  • S Shaw

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.

Details

Original languageEnglish
Pages (from-to)7144-8
Number of pages5
JournalNational Academy of Sciences. Proceedings
Volume91
Issue number15
Publication statusPublished - 19 Jul 1994

Keywords

  • Cell Adhesion, Cell Movement, Chemokine CCL4, Cytokines, Cytoskeleton, Hepatocyte Growth Factor, Macrophage Inflammatory Proteins, Monokines, Phosphorylation, Polymerase Chain Reaction, Proto-Oncogene Proteins c-met, Receptor Protein-Tyrosine Kinases, T-Lymphocyte Subsets, Tyrosine