HEPARIN IS AN ADHESIVE LIGAND FOR THE LEUKOCYTE INTEGRIN MAC-1 (CD11BCD18)/

Previous studies have demonstrated that the leukocyte integrin Mac-1 a dheres to several cell surface and soluble ligands including intercell ular adhesion molecule-1, fibrinogen, iC3b, and factor X. However, exp eriments with Mac-1-expressing transfectants, purified Mac-1, and mAbs to Mac-1 indicate the existence of additional ligands. In this paper, we demonstrate a direct interaction between Mac-1 and heparan sulfate glycans. Heparin affinity resins immunoprecipitate Mac-1, and neutrop hils and transfectant cells that express Mac-1 bind to heparin and hep aran sulfate, but not to other sulfated glycosaminoglycans. Inhibition studies with mAbs and chemically modified forms of heparin suggest th e I domain as a recognition site on Mac-1 for heparin, and suggest tha t either N- or O-sulfation is sufficient for heparin to bind efficient ly to Mac-1. Under conditions of continuous flow in which heparins and E-selectin are cosubstrates, neutrophils tether to E-selectin and for m firm adhesions through a Mac-1-heparin interaction.