CC BY-NC-ND 4.0 · Thromb Haemost 2022; 122(05): 767-776
DOI: 10.1055/a-1659-6214
Cellular Haemostasis and Platelets

Characterization of the Role of Integrin α5β1 in Platelet Function, Hemostasis, and Experimental Thrombosis

Emily Janus-Bell*
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Alexandra Yakusheva*
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
2   Center for Theoretical Problems of Physicochemical Pharmacology, Cellular Hemostasis Lab, Moscow, Russia
,
Cyril Scandola
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Nicolas Receveur
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Usman Muhammad Ahmed
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Clarisse Mouriaux
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Catherine Bourdon
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Cécile Loubière
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Anita Eckly
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Yotis A. Senis
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Mikhail A. Panteleev
2   Center for Theoretical Problems of Physicochemical Pharmacology, Cellular Hemostasis Lab, Moscow, Russia
,
Christian Gachet
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
,
Pierre H. Mangin
1   Université de Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, FMTS, Strasbourg, France
› Author Affiliations
Funding This work was supported by INSERM, EFS, ARMESA (Association de Recherche et Développement en Médecine et Santé Publique), and SFH (Société Française d'Hématologie). The reported study was funded by RFBR, project number 19-34-9003 9.

Abstract

Objective Integrins are key regulators of various platelet functions. The pathophysiological importance of most platelet integrins has been investigated, with the exception of α5β1, a receptor for fibronectin. The aim of this study was to characterize the role of α5β1 in megakaryopoiesis, platelet function, and to determine its importance in hemostasis and arterial thrombosis.

Approach and Results We generated a mouse strain deficient for integrin α5β1 on megakaryocytes and platelets (PF4Cre-α5−/−). PF4Cre-α5−/− mice were viable, fertile, and presented no apparent signs of abnormality. Megakaryopoiesis appears unaltered as evidence by a normal megakaryocyte morphology and development, which is in agreement with a normal platelet count. Expression of the main platelet receptors and the response of PF4Cre-α5−/− platelets to a series of agonists were all completely normal. Adhesion and aggregation of PF4Cre-α5−/− platelets under shear flow on fibrinogen, laminin, or von Willebrand factor were unimpaired. In contrast, PF4Cre-α5−/− platelets displayed a marked decrease in adhesion, activation, and aggregation on fibrillar cellular fibronectin and collagen. PF4Cre-α5−/− mice presented no defect in a tail-bleeding time assay and no increase in inflammatory bleeding in a reverse passive Arthus model and a lipopolysaccharide pulmonary inflammation model. Finally, no defects were observed in three distinct experimental models of arterial thrombosis based on ferric chloride-induced injury of the carotid artery, mechanical injury of the abdominal aorta, or laser-induced injury of mesenteric vessels.

Conclusion In summary, this study shows that platelet integrin α5β1 is a key receptor for fibrillar cellular fibronectin but is dispensable in hemostasis and arterial thrombosis.

Author Contributions

A.Y., C.S., E.J.B., and N.R. acquired, analyzed, and interpreted the data and wrote the manuscript; C.B., C.L., C.M., and U.M.A. acquired and analyzed the data; A.E., M.A.P., and Y.A.S. designed the research, interpreted the data, and wrote the manuscript; C.G. contributed to writing of the manuscript; P.H.M. conceived and designed the research, interpreted the data, wrote the manuscript, and handled funding and supervision.


* These authors contributed equally to this work.


Supplementary Material



Publication History

Received: 04 May 2021

Accepted: 03 August 2021

Accepted Manuscript online:
01 October 2021

Article published online:
10 November 2021

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