Minimal platelet deposition and activation in models of injured vessel wall ensure optimal neutrophil adhesion under flow conditions

Platelets at injured vessel wall form an adhesive surface for leukocyte adh esion. The precise relation between platelet adhesion and activation and le ukocyte adhesion, however, is not known. We therefore used various models o f injured vessel wall to form different patterns of platelet adhesion. The interaction of polymorphonuclear neutrophils (PMNs) was subsequently studie d under flow conditions. In the absence of platelets, not only endothelial cell, smooth muscle cell, and fibroblast matrices but also purified matrix proteins (fibrinogen, collagen, and fibronectin) barely support PMN adhesio n. The presence of platelets, however, strongly enhances PMN adhesion. PMN adhesion shows a proportional increase with platelet coverage up to 15%. Al though PMNs roll over the scarcely scattered platelets, they speed up again when encountering surfaces without platelets. This "hopping" interaction o f PMNs vanishes with platelet coverage >15%. Unobstructed rolling of PMNs i s than observed and soon leads to a maximal adhesion of 1000 to 1200 cells/ mm(2). The mean rolling velocity of PMNs continues to decrease with higher platelet coverage. Platelet aggregate formation is an accepted indicator of platelet activation. The presence of platelet aggregates instead of contac t or spread platelets, however, does not increase PMN adhesion. Also, addit ional stimulation of surface-associated platelets by thrombin fails to infl uence PMN adhesion, Moreover, indomethacin as an inhibitor of platelet acti vation and aggregation does not change the subsequent PMN interaction. In c onclusion, approximately 15% of platelet coverage is sufficient for optimal PMN adhesion. Increasing platelet coverage increases the availability of p latelet-associated receptors that lower PMN rolling velocity. Additional ac tivation of adherent platelets makes no difference in the expression of rel evant adhesion receptors. Therefore, minimal vascular damage in vivo and on ly scarce platelet adhesion will already evoke significant colocalization o f leukocytes.