The C–C Chemokine MCP-1 Differentially Modulates the Avidity of b1 and b2 Integrins on T Lymphocytes

cytes into inflammatory sites in vivo (Bargatze and The ability of chemokines, particularly MCP-1, to inButcher, 1993; Spangrude et al., 1985). This implicates duce integrin-dependent binding of T lymphocytes to a G protein–coupled signaling event in lymphocyte adendothelial adhesion molecules or extracellular matrix hesion and extravasation and suggests a role for chem(ECM) components was examined. MCP-1 induced oattractants, since all chemoattractant receptors thus significant adhesion to fibronectin (FN) and to endofar identified couple to G proteins (Gerard and Gerard, thelial-secreted ECM but not to purified ICAM-1 or 1994; Murphy, 1994). Moreover, several chemokines VCAM-1, or to activated endothelium. The MCP-1have been shown to up-regulate lymphocyte adhesion induced binding of T lymphocytes to FN was rapid, to endothelial cells or isolated endothelial ligands (Taub dose dependent, and resulted from activation of both et al., 1993a, 1993b; Tanaka et al., 1993b), although VLA-4 and VLA-5. Like MCP-1, the chemokines these proadhesive effects were relatively small and reRANTES and MIP-1b induced T lymphocyte binding to quired relatively long incubation times. FN, but not to ICAM-1. We suggest, therefore, that Interestingly, while both neutrophils and T lymphothese T lymphocyte chemokines may be most imporcytes express b2 integrins that bind to ICAM-1 and tant, not in initiating integrin-dependent firm adhesion ICAM-2 expressed on vascular endothelium, T lymphoof T lymphocytes to the vascular wall, but rather, in cytes also express the b1 integrin, VLA-4, which binds subsequent adhesive interactions during migration to VCAM-1, expressed on stimulated endothelium, as into tissue. well as fibronectin (FN) expressed in the subendothelial