Neutrophil Interactions with Adherent Platelets

We have studied the pathways that lead to arrest and firm adhesion of rolling PMN on activated, surface-adherent platelets. Stable arrest and adhesion strengthening of PMN on thrombin-stimulated, surface-adherent platelets in flow required distinct Ca 2 1 and Mg 2 1 -dependent regions of Mac-1 ( a M b 2), and involved interactions of Mac-1 with fibrinogen, which was bound to platelets via a IIb b 3. Mac-1 also bound to other unidentified ligands on platelets, which were not intracellular 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 a IIb b 3 from a patient with Glanzmann thrombasthenia. Tethering of PMN on platelet ICAM-2 via LFA-1 ( a L b 2) was observed, which may facilitate the transition between rolling on selectins 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 firm adhesion. ( J. Clin. Invest. 1997. 100:2085–2093.)