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.
Original language | English |
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Pages (from-to) | 7144-8 |
Number of pages | 5 |
Journal | National Academy of Sciences. Proceedings |
Volume | 91 |
Issue number | 15 |
Publication status | Published - 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