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 reac-(320 mPa). ECM coated with both platelets and fibrin induced more static and shear-resistant PMN adhesion. PMN tion involves platelet and fibrin deposition. At these sites, circulating leukocytes marginate and become activated. Ad-adhesion to fibrin alone but not to platelet/fibrin surfaces was inhibited by soluble fibrinogen. Adhesion to fibrin alone hered platelets can support leukocyte localization; however, the role of fibrin in this respect is not known. We studied was inhibited by CD11b and CD18 blocking antibodies. Furthermore, fibrin formed under flow conditions showed up to the adhesion of human neutrophils (polymorphonuclear leukocytes [PMNs]) to endothelial extracellular matrix (ECM)-threefold higher PMN adhesion compared with fibrin formed under static conditions, due to structural differences. These bound fibrin and platelets under flow conditions. ECM alone did not show PMN adhesion. ECM-coated cover slips were results indicate that circulating PMNs adhere to fibrin in an integrin-dependent manner at moderate shear stresses. perfused with plasma to form a surface-bound fibrin network, and/or with whole blood to allow platelet adhesion.However, at higher shear rates (Û200 mPa), additional mechanisms (ie, activated platelets) are necessary for an interac-Unstimulated PMNs adhered to fibrin at moderate shear stress (20 to 200 mPa). ECM-bound platelets induced rolling tion of PMNs with a fibrin network.

NEWASPECTSINTHEPATHOGENESISANDTREATMENTOFTHROMBOTICTHROMBOCYTOPENICPURPURAANDHEMOLYTICUREMICSYNDROME

“…This possible mechanism is consistent with the observation that high neutrophil count is a poor prognostic indicator in Stx‐associated HUS (16). Several other experiments (17, 18) have shown that Stx stimulation induces expression of adhesion molecules and neutrophil adhesion on endothelium, and that platelets and fibrin, a characteristic part of TM lesions, can facilitate neutrophil adherence (19, 20). The latter mechanisms could further facilitate delivery of Stx to endothelial cells.…”

Extracellular Matrix‐Based Strategies for Immunomodulatory Biomaterials Engineering

“…Fibrin is formed by the polymerization of its circulating precursor, fibrinogen, which is cleaved by activated thrombin in the terminal step of the coagulation cascade. Polymerization is thought to expose integrin‐binding sites including RGD, P1 and P2 peptides, which promote the adhesion of immune cells via αmβ2 . Platelets also bind to fibrin through αiibβ3 (GP2b3a), ɑvβ1, and P‐selectin, further stabilizing the clot.…”

Neutrophils mediate edema formation but not mechanical allodynia during zymosan-induced inflammation

“…Therefore, it cannot be ruled out that neutrophil depletion induced an inflammatory answer in the mice that alters the inflammatory response to zymosan injection in the paw. To circumvent neutrophil depletion and activation of the immune system, we used in second-approach antibodies, which are able to block receptors on neutrophils without depleting these cells [25][26][27]. We chose antibodies against CD162 and CD11b, as both receptors are known to mediate neutrophil recruitment to inflammation sites [26,28,29].…”