The Platelet Glycoprotein IIb/IIIa Complex Is lnvolved in the Adhesion of Activated Platelets to Leukocytes

Abstract

SummaryThe adhesion of activated platelets to leukocytes (rosette formation) seems to be mediated by CD62 on platelets and its counterreceptor (CD 15 or a sialic acid-containing glycoprotein) on polymorphonuclear leukocytes (PMNL). However, neither treatment of platelets with an anti-CD62 antibody or fucoidan nor treatment of PMNL with anti-CD15 antibody or neuraminidase are able to inhibit completely the adhesion. Therefore, we have studied the platelet GPIIb/IIIa complex (CD41a) for its involvement in the adhesion of activated platelets to PMNL. The following evidences point to a participation of CD41a in the adhesion of activated platelets to leukocytes: a) inhibition of adhesion by monoclonal antibodies (mab) raised toward CD41a, b) inhibition of adhesion by peptides such as RGDS and echistatin, c) inhibition of adhesion by dissociation of the CD41a complex with EGTA, and d) inhibition of rosette formation using platelets from a thrombasthenic patient which have almost no CD41a in the surface membrane but a normal expression of CD62. It is likely that fibrinogen is involved in the adhesion of platelets to PMNL via CD41a, since fibrinogen increases the rosette formation of ADP-stimulated platelets. Furthermore, the incubation of unstimulated platelets with fibrinogen and an antibody raised against glycoprotein III a which stimulates fibrinogen binding to the platelet surface results in an enlarged rosette formation.

Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to alphaIIbbeta3 and stimulated by platelet-activating factor.

“…Our results in flow expand on previous evidence demonstrating the involvement of fibrinogen and ␣IIb␤3 in the adhesion of activated platelets to leukocytes in stasis (52), and implicating fibrinogen in platelet-PMN interactions in cell suspension or whole blood (15). However, we did not observe a complete inhibition of PMN accumulation and adhesion strengthening in flow with antifibrinogen F(abЈ)2 in combination with ICAM-2 mAb, peptides, or 7E3 mAb.…”

Selectin Blockade Reduces Neutrophil Interaction With Platelets at the Site of Deep Arterial Injury by Angioplasty in Pigs

“…In the absence of endothelium, it has been shown that neutrophils can roll on immobilized platelets 19 or adhere via platelet P-selectin 21 or neutrophil ␤ 2 -integrin. 43 Many studies have reported that other mechanisms may be implicated in platelet binding to neutrophils, such as (1) fibrinogen bridging via platelet GPIIb/IIIa and neutrophil MAC-1, 44,45 (2) thrombospondin bridging via GPIa/IIa, GPIIb/IIIa, or GPIV on platelets and a specific receptor on neutrophils, 46,47 (3) platelet ICAM-1 binding to neutrophil LFA-1, 48 and (4) immune complex interactions between platelet Fc RII (CD32) and neutrophil Fc RIIIb (CD16). 49 These different mechanisms for neutrophil interactions with platelet and recruitment to damaged arterial surfaces may explain the lack of complete inhibition, by CY-1503, of neutrophil adhesion in our study.…”

P-selectin and MAC-1 mediate monocyte rolling and adhesion to ECM-bound platelets under flow conditions

“…It is tempting to speculate that monocyte activation takes place during the tethering and initial interaction with platelets, leading to a high-affinity state of integrins for their ligands. In support of this concept is the finding that binding of P-selectin or activated platelets to monocytes induces intracellular signaling and activation [39][40][41].…”