Factor XIII mediates adhesion of platelets to endothelial cells through αvβ3 and glycoprotein IIb/IIIa integrins

R. Dardik, B. Shenkman, I. Tamarin, R. Eskaraev, J. Hársfalvi, D. Varon, A. Inbal

Research output: Contribution to journalArticle

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Abstract

Coagulation factor XIII (FXIII) is a transglutaminase that catalyzes crosslink formation in fibrin clots. Endothelial cells (EC) were demonstrated to bind FXIII via their αvβ3 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 inihibited by the monoclonal antibody L609 against αvβ3 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-αvβ3 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 αvβ3 and platelet GPIIb/IIIa integrins. This interaction may be relevant for tissue remodeling and wound repair after vascular injury in FXIII-deficient patients.

Original languageEnglish
Pages (from-to)317-323
Number of pages7
JournalThrombosis Research
Volume105
Issue number4
DOIs
Publication statusPublished - Feb 15 2002

Fingerprint

Factor XIII
Platelet Glycoprotein GPIIb-IIIa Complex
Integrins
Blood Platelets
Endothelial Cells
Factor XIIIa
Integrin beta3
Transglutaminases
Vascular System Injuries
Fibrinolysin
Adenine
Fibrin
Intravenous Infusions
Cell Communication

Keywords

  • αβ
  • Endothelial cells
  • FXIII
  • GPIIb/IIIa
  • Platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Hematology

Cite this

Factor XIII mediates adhesion of platelets to endothelial cells through αvβ3 and glycoprotein IIb/IIIa integrins. / Dardik, R.; Shenkman, B.; Tamarin, I.; Eskaraev, R.; Hársfalvi, J.; Varon, D.; Inbal, A.

In: Thrombosis Research, Vol. 105, No. 4, 15.02.2002, p. 317-323.

Research output: Contribution to journalArticle

Dardik, R. ; Shenkman, B. ; Tamarin, I. ; Eskaraev, R. ; Hársfalvi, J. ; Varon, D. ; Inbal, A. / Factor XIII mediates adhesion of platelets to endothelial cells through αvβ3 and glycoprotein IIb/IIIa integrins. In: Thrombosis Research. 2002 ; Vol. 105, No. 4. pp. 317-323.
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AU - Varon, D.

AU - Inbal, A.

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N2 - Coagulation factor XIII (FXIII) is a transglutaminase that catalyzes crosslink formation in fibrin clots. Endothelial cells (EC) were demonstrated to bind FXIII via their αvβ3 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 inihibited by the monoclonal antibody L609 against αvβ3 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-αvβ3 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 αvβ3 and platelet GPIIb/IIIa integrins. This interaction may be relevant for tissue remodeling and wound repair after vascular injury in FXIII-deficient patients.

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