CHEMOKINES REGULATE T-CELL ADHERENCE TO RECOMBINANT ADHESION MOLECULES AND EXTRACELLULAR-MATRIX PROTEINS

Chemokines are a family of structurally related, low m.w. proteins tha t regulate leukocyte migration both in vitro and in vivo, By virtue of their target cell specificity, chemokines have the potential to selec tively recruit leukocyte subpopulations into sites of inflammation dur ing the genesis of an immune response. Chemokines have been shown to i nduce leukocyte adhesion to endothelium, to facilitate trans-endotheli al passage, and to direct cell migration along a protein gradient (che motaxis), The chemokines (macrophage inflammatory protein-1 alpha, mac rophage inflammatory protein-1 beta, RANTES, and IFN-inducible protein -10) have recently been reported to be chemotactic for T cells, We hav e investigated the potential activity of these proteins in regulation of T cell adhesion. These chemokines induce T cell adhesion to purifie d, recombinant human adhesion molecules (rhlCAM-1, rhVCAM-1) and to EC M 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 adhesi on is not associated with an increased surface expression of adhesion proteins, suggesting that chemokines stimulate the development of a hi gh affinity state in the integrin molecules, Our findings provide in v itro evidence of a critical role for chemokines in T cell adhesion to endothelial adhesion molecules and ECM proteins, thereby promoting hap totactic migration of T cells to sites of inflammation in vivo.