Platelet and Fibrin Deposition at the Damaged Vessel Wall: Cooperative Substrates for Neutrophil Adhesion Under Flow Conditions

Abstract

At sites of vessel wall damage, the primary hemostatic reaction involves platelet and fibrin deposition. At these sites, circulating leukocytes marginate and become activated. Adhered platelets can support leukocyte localization; however, the role of fibrin in this respect is not known. We studied the adhesion of human neutrophils (polymorphonuclear leukocytes [PMNs]) to endothelial extracellular matrix (ECM)-bound fibrin and platelets under flow conditions. ECM alone did not show PMN adhesion. ECM-coated cover slips were perfused with plasma to form a surface-bound fibrin network, and/or with whole blood to allow platelet adhesion. Unstimulated PMNs adhered to fibrin at moderate shear stress (20 to 200 mPa). ECM-bound platelets induced rolling adhesion and allowed more PMNs to adhere at higher shear (320 mPa). ECM coated with both platelets and fibrin induced more static and shear-resistant PMN adhesion. PMN adhesion to fibrin alone but not to platelet/fibrin surfaces was inhibited by soluble fibrinogen. Adhesion to fibrin alone was inhibited by CD11b and CD18 blocking antibodies. Furthermore, fibrin formed under flow conditions showed up to threefold higher PMN adhesion compared with fibrin formed under static conditions, due to structural differences. These results indicate that circulating PMNs adhere to fibrin in an integrin-dependent manner at moderate shear stresses. However, at higher shear rates (<200 mPa), additional mechanisms (ie, activated platelets) are necessary for an interaction of PMNs with a fibrin network.

Circulating platelet–neutrophil complexes represent a subpopulation of activated neutrophils primed for adhesion, phagocytosis and intracellular killing

“…This may be explained by considering the role of neutrophil integrins in complex formation. A number of groups have observed the capacity of immobilized platelets to bind leucocytes (including neutrophils) via a multistep selectin and b2 integrin dependent mechanism (Kuijper et al, 1996(Kuijper et al, , 1997Buttrum et al, 1993;Diacovo et al, 1996), analogous to that which occurs between activated endothelium and leucocytes. Platelet CD62P, platelet-derived PAF and neutrophil b2-integrin activation have recently been described as requirements for maximal adhesion of neutrophils on immobilized platelets (Evangelista et al, 1996).…”

High‐density lipoprotein: A potent inhibitor of inflammation

“…27 However, there may be a far more complex mechanism underlying the reduction in thrombus formation. It has been shown that neutrophils can facilitate the capture and adhesion of platelets to aid in the formation of a thrombus; [55][56][57] thus, a synergistic pathway for HDL may exist, acting to inhibit platelets, leucocytes and possibly endothelial cells if they remain intact, which is unlikely in the FeCl 3 model or sites of plaque rupture. 58 ''modulates these effects through SR-BI'' Ó 2010 The Authors Journal compilation Ó 2010 Blackwell Publishing Asia Pty Ltd Attenuation of thrombus formation and size by HDL may be beneficial in the context of plaque rupture, where inhibition of vessel occlusion is desirable.…”

Comparison of New Technology Integrated and Nonintegrated Arterial Filters Used in Cardiopulmonary Bypass Surgery: A Randomized, Prospective, and Single Blind Study

“…No correlation between duration of cross-clamping and cell activation was found [ 13 ]. Platelets deposited on endothelial cells recruit leukocytes at shear rates that otherwise do not allow leukocyte adhesion [ 14 ]. Rinder et al reported that, in addition to an increased number of activated leukocytes, the number of leukocyte-platelet conjugates was increased in patients undergoing cardiac surgery with CPB [ 15 ].…”