CHEMOKINES AND THE ARREST OF LYMPHOCYTES ROLLING UNDER FLOW CONDITIONS

Circulating lymphocytes are recruited from the blood to the tissue by railing along the endothelium until being stopped by a signaling event linked to the G(i) alpha subunit of a heterotrimeric GTP-binding prot ein; that event then triggers rapid integrin-dependent adhesion. Four chemokines are now shown to induce such adhesion tb intercellular adhe sion molecule-1 and to induce arrest of rolling cells within 1 second under flow conditions similar to those of blood. SDF-1 (also called PB SF), 6-C-kine (also called Exodus-2), and MIP-3 beta (also called ELC or Exodus-3) induced adhesion of most circulating lymphocytes, includi ng most CD4(+) T cells; and MIP-3 alpha (also called LARC or Exodus-1) triggered adhesion of memory, but not nai ve, CD4(+) T cells. Thus, c hemokines can regulate the arrest of lymphocyte subsets under flawing conditions, which may allow them to control lymphocyte-endothelial cel l recognition and lymphocyte recruitment in vivo.