NEUTROPHIL ACCUMULATION ON ACTIVATED, SURFACE-ADHERENT PLATELETS IN FLOW IS MEDIATED BY INTERACTION OF MAC-1 WITH FIBRINOGEN BOUND TO ALPHA-IIB-BETA-3 AND STIMULATED BY PLATELET-ACTIVATING-FACTOR

We have studied the pathways that lead to arrest and firm adhesion of rolling PMN on activated, surface-adherent platelets, Stable arrest an d adhesion strengthening of PMN on thrombin-stimulated, surface-adhere nt platelets in flow required distinct Ca2+- and Mg2+-dependent region s of Mac-1 (alpha M beta 2), and involved interactions of Mac-1 with f ibrinogen, which was bound to platelets via alpha IIb beta 3. Mac-1 al so bound to other unidentified ligands on platelets, which were not in tracellular adhesion molecule-2 (ICAM-2), heparin, or heparan-sulfate proteoglycans, This was shown by inhibition with mAbs or peptides, by treatment of platelets with heparitinase, and by using platelets with defective alpha IIB beta 3 from a patient with Glanzmann thrombastheni a. Tethering of PMN on platelet ICAM-2 via LFA-1 (alpha L beta 2) was observed, which may facilitate the transition between rolling on selec tins and Mac-1-dependent arrest. Arrest and adhesion strengthening was pertussis toxin sensitive and in flow was mainly induced by platelet- activating factor but not through activation of the chemokine receptor CXCR2. In stasis, spreading occurred and the CXCR2 contributed to fir m adhesion.