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Impaired thrombin generation in R eelin‐deficient mice: a potential role of plasma R eelin in hemostasis
Author(s) -
Tseng W.L.,
Chen T.H.,
Huang C.C.,
Huang Y.H.,
Yeh C.F.,
Tsai H.J.,
Lee H.Y.,
Kao C.Y.,
Lin S.W.,
Liao H.R.,
Cheng J.C.,
Tseng C.P.
Publication year - 2014
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12736
Subject(s) - reelin , hemostasis , thrombin , chemistry , platelet , dab1 , fibrinogen , coagulation , fibrin , receptor , microbiology and biotechnology , endocrinology , medicine , immunology , biochemistry , biology
Summary Background Reelin is a large extracellular glycoprotein that is present in the peripheral blood. That R eelin interacts with the coagulation components and elicits a functional role in hemostasis has not yet been elucidated. Objectives The hemostatic activity of R eelin is investigated and defined in this study. Methods The interplay of R eelin with coagulation components was elucidated by far ‐W estern and liposome/platelet binding assays. In vivo and ex vivo hemostasis‐related analyses of R eelin‐deficient mice and plasma were also performed. Results Reelin interacted with the liposomes containing phosphatidylserine ( PS ) or phosphatidylcholine. Instead of interacting with known Reelin receptors ( A po E receptor 2, very low density lipoprotein receptor and integrin β1), Reelin interacted with PS of the activated platelets. The interaction between Reelin and the coagulation factors of thrombin and FX a was also demonstrated with the K d of 11.7 and 21.2 n m , respectively. Reelin‐deficient mice displayed a prolonged bleeding time and an increase in rebleeding rate. Despite the fact that Reelin deficiency had no significant effect on the clotting time of prothrombin and activated partial thromboplastin time, the fibrin clot formation was abnormal and the fibrin clot structure was relatively loosened with reduced clot strength. Abnormal fibrinogen expression did not account for the hemostatic defects associated with Reelin deficiency. Instead, thrombin generation was impaired concomitant with an altered prothrombin cleavage pattern. Conclusions By interacting with platelet phospholipids and the coagulation factors, thrombin and FX a, Reelin plays a selective role in coagulation activation, leading to thrombin generation and formation of a normal fibrin clot.