Thromb Haemost
DOI: 10.1055/s-0039-1683912
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Binding of Coagulation Factor XIII Zymogen to Activated Platelet Subpopulations: Roles of Integrin αIIbβ3 and Fibrinogen

Yana N. Kotova*
1  Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia
2  Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
,
Nadezhda A. Podoplelova*
1  Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia
2  Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
,
Sergey I. Obydennyy
1  Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia
2  Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
,
Elizaveta A. Kostanova
3  Emmanuel Institute of Biochemical Physics, Russian Academy of Science, Moscow, Russia
,
Alexander A. Ryabykh
2  Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
,
Aleksandra S. Demyanova
1  Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia
,
Maria I. Biriukova
3  Emmanuel Institute of Biochemical Physics, Russian Academy of Science, Moscow, Russia
,
Mark A. Rosenfeld
3  Emmanuel Institute of Biochemical Physics, Russian Academy of Science, Moscow, Russia
,
Alexey V. Sokolov
4  Institute of Experimental Medicine, St. Petersburg, Russia
5  Chair of Fundamental Problems of Medicine, Saint Petersburg State University, St. Petersburg, Russia
,
Herve Chambost
6  INSERM, INRA, C2VN, Aix-Marseille Université, Marseille, France
,
Maria A. Kumskova
7  National Research Center for Hematology, Moscow, Russia
,
Fazoil I. Ataullakhanov
1  Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia
2  Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
8  Faculty of Physics, Moscow State University, Moscow, Russia
,
Marie-Christine Alessi
5  Chair of Fundamental Problems of Medicine, Saint Petersburg State University, St. Petersburg, Russia
,
Mikhail A. Panteleev
1  Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia
2  Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
8  Faculty of Physics, Moscow State University, Moscow, Russia
9  Faculty of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
› Author Affiliations
Funding This study was supported by the grant from the endowment foundation «Doctors, innovations, science for children», and by the Russian Foundation for Basic Research grants 16-04-00125, 17-00-00140, 17-04-01309, 18-34-20026 and 19-04-00615.
Further Information

Publication History

28 September 2018

04 February 2019

Publication Date:
01 April 2019 (eFirst)

Abstract

Factor XIIIa (fXIIIa) is a transglutaminase that plays a crucial role in fibrin clot stabilization and regulation of fibrinolysis. It is known to bind to procoagulant platelets. In contrast, the zymogen fXIII interaction with platelets is not well characterized. We investigated the interaction of zymogen fXIII with activated platelet subpopulations. Confocal microscopy and flow cytometry using fluorescently labelled factors and antibodies. Phosphatidylserine (PS)-positive activated platelets bound 700 to 800 molecules/cell of fXIII at 100 nM, while both PS-negative activated platelets and resting platelets bound 200 to 400 molecules/cell. The binding was reversible, calcium-independent and linear within the fXIII concentration range of up to 1,000 nM. fXIII predominantly bound to the caps of procoagulant platelets and co-localized with fibrinogen. Exogenous fibrinogen promoted fXIII binding by activated PS-negative platelets; this effect was abolished by the integrin αIIbβ3 antagonist monafram. The fXIII binding was 1.5- to 3-fold decreased for platelets from four patients with grey platelet syndrome, and was variable for platelets from six patients with Glanzmann's thrombasthenia. Strong platelet stimulation, fibrinogen and αIIbβ3 play essential roles in fXIII binding, without any of them fXIII does not bind to platelets. The preferential binding in the cap-like structures might be important for increasing local fXIII concentration in platelet thrombi.

Authors' Contributions

Y.N.K., N.A.P., S.I.O., E.A.K., A.A.R., A.S.D., M.I.B., M.A.R. and A.V.S. performed experiments and analysed data. H.C., M.A.K. and M.C.A. recruited and characterized patients. M.C.A., F.I.A. and M.A.P. planned research and analysed the data. Y.N.K., N.A.P., M.C.A. and M.A.P. wrote the paper.


* These authors contributed equally to this work.


Supplementary Material