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 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.
Adams
D H
DH
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Harvath
L
L
Bottaro
D P
DP
Interrante
R
R
Catalano
G
G
Tanaka
Y
Y
Strain
A
A
Hubscher
S G
SG
Shaw
S
S
D002448:Cell Adhesion; D002465:Cell Movement; D054407:Chemokine CCL4; D016207:Cytokines / Q000737:chemistry / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D014443:Tyrosine / Q000378:metabolism
D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D014443:Tyrosine; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases