Factor XIII mediates adhesion of platelets to endothelial cells through alpha(v)beta(3) and glycoprotein IIb/IIIa integrins

• Published in: Thrombosis research 2002-02, Vol.105 (4), p.317-323
• Main Authors: Dardik, R, Shenkman, B, Tamarin, I, Eskaraev, R, Harsfalvi, J, Varon, D, Inbal, A
• Format: Article
• Language: English
• Subjects: Cell Line; Endothelium, Vascular - physiology; Factor XIII - pharmacology; Factor XIII - physiology; Factor XIII Deficiency - blood; Factor XIIIa - physiology; Humans; In Vitro Techniques; Integrin alphaVbeta3 - blood; Platelet Adhesiveness - drug effects; Platelet Adhesiveness - physiology; Platelet Glycoprotein GPIIb-IIIa Complex - physiology; Solubility
• ISSN: 0049-3848
• DOI: 10.1016/S0049-3848(02)00014-2

Coagulation factor XIII (FXIII) is a transglutaminase that catalyzes crosslink formation in fibrin clots. Endothelial cells (EC) were demonstrated to bind FXIII via their alpha(v)beta3 integrin receptor. FXIII was also shown to bind platelet glycoprotein IIb/IIIa receptor. In the present study, we analyzed if FXIII can mediate platelet-EC interaction. Both FXIII and activated FXIII (FXIIIa) bound to EC monolayers; this binding was enhanced by the addition of Mn2+ and was inhibited by the monoclonal antibody L609 against alpha(v)beta3 integrin. Normal washed platelets also bound surface-immobilized or soluble FXIII and FXIIIa, and the binding was GPIIb/IIIa dependent. The effect of FXIII concentrate (Fibrogammin-P) treatment on the interaction of ECs with platelets from six FXIII-deficient patients was studied. Patients' platelets were radiolabeled with 3H-Adenine, washed, resuspended in autologous plasma and allowed to adhere to immortalized EC line EAhy926. Adhesion of platelets from FXIII-deficient patients to ECs increased 1.7+/-0.4-fold (P=.01) following intravenous infusion of FXIII concentrate. Similarly, addition of 1 U/ml of FXIII concentrate to the patients' PRP in vitro increased the adhesion 1.8+/-0.5-fold (P=.008). Preincubation of the EC monolayers with increasing concentrations of either FXIII or FXIIIa augmented the adhesion of normal washed platelets to ECs in a dose-dependent manner. At 10 U/ml of EC-bound FXIII or FXIIIa, platelet adhesion enhanced 1.7+/-0.25-fold (P=.03) and 2.5+/-0.5-fold (P=.02), respectively. The increase in platelet adhesion was completely abolished by pretreatment of ECs with the anti-alpha(v)beta3 antibody L609 or by preincubation of the platelets with the GPIIb/IIIa inhibitor Abciximab. Taken together, our data indicate that FXIII mediates the interaction of platelets with ECs by bridging between endothelial alpha(v)beta3 and platelet GPIIb/IIIa integrins. This interaction may be relevant for tissue remodeling and wound repair after vascular injury in FXIII-deficient patients.