Image_2_Complement C1q Enhances Primary Hemostasis.TIF (559.98 kB)

Image_2_Complement C1q Enhances Primary Hemostasis.TIF

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posted on 16.07.2020, 04:07 by Claudia Donat, Robert Kölm, Kinga Csorba, Eylul Tuncer, Dimitrios A. Tsakiris, Marten Trendelenburg

The cross-talk between the inflammatory complement system and hemostasis is becoming increasingly recognized. The interaction between complement C1q, initiation molecule of the classical pathway, and von Willebrand factor (vWF), initiator molecule of primary hemostasis, has been shown to induce platelet rolling and adhesion in vitro. As vWF disorders result in prolonged bleeding, a lack of C1q as binding partner for vWF might also lead to an impaired hemostasis. Therefore, this study aimed to investigate the in vivo relevance of C1q-dependent binding of vWF in hemostasis. For this purpose, we analyzed parameters of primary and secondary hemostasis and performed bleeding experiments in wild type (WT) and C1q-deficient (C1qa−/−) mice, with reconstitution experiments of C1q in the latter. Bleeding tendency was examined by quantification of bleeding time and blood loss. First, we found that complete blood counts and plasma vWF levels do not differ between C1qa−/− mice and WT mice. Moreover, platelet aggregation tests indicated that the platelets of both strains of mice are functional. Second, while the prothrombin time was comparable between both groups, the activated partial thromboplastin time was shorter in C1qa−/− mice. In contrast, tail bleeding times of C1qa−/− mice were prolonged accompanied by an increased blood loss. Upon reconstitution of C1qa−/− mice with C1q, parameters of increased bleeding could be reversed. In conclusion, our data indicate that C1q, a molecule of the first-line of immune defense, actively participates in primary hemostasis by promoting arrest of bleeding. This observation might be of relevance for the understanding of thromboembolic complications in inflammatory disorders, where excess of C1q deposition is observed.

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