Chemokines regulate T cell adherence to recombinant adhesion molecules and extracellular matrix proteins.
Chemokines are a family of structurally related, low m.w. proteins that regulate leukocyte migration both in vitro and in vivo. By virtue of their target cell specificity, chemokines have the potential to selectively recruit leukocyte subpopulations into sites of inflammation during the genesis of an immune response. Chemokines have been shown to induce leukocyte adhesion to endothelium, to facilitate trans-endothelial passage, and to direct cell migration along a protein gradient (chemotaxis). The chemokines (macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, RANTES, and IFN-inducible protein-10) have recently been reported to be chemotactic for T cells. We have investigated the potential activity of these proteins in regulation of T cell adhesion. These chemokines induce T cell adhesion to purified, recombinant human adhesion molecules (rhICAM-1, rhVCAM-1) and to ECM proteins: fibronectin, collagen, and laminin. The chemokine-induced adhesion process occurs rapidly, is dose-dependent, and appears to be mediated via beta 1 and beta 2 integrins. The enhanced T cell adhesion is not associated with an increased surface expression of adhesion proteins, suggesting that chemokines stimulate the development of a high affinity state in the integrin molecules. Our findings provide in vitro evidence of a critical role for chemokines in T cell adhesion to endothelial adhesion molecules and ECM proteins, thereby promoting haptotactic migration of T cells to sites of inflammation in vivo.
Lloyd
A R
AR
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21702, USA.
Oppenheim
J J
JJ
Kelvin
D J
DJ
Taub
D D
DD
D018821:CD18 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005353:Fibronectins / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D016029:Receptors, Very Late Antigen / Q000502:physiology; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D018821:CD18 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D018925:Chemokines; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019012:Integrin beta1; D016029:Receptors, Very Late Antigen; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1