Complement C1q Enhances Primary Hemostasis

Abstract

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.

Serum proteomic profiling in patients with advanced Schistosoma japonicum-induced hepatic fibrosis

“…5 ), the proteins complement C1q subcomponent subunit A (C1QA, 1.82-fold) and complement factor D (CFD, 2.51-fold) were differentially expressed in the SHF-F4 and SHF-F2 groups of schistosomiasis patients. C1QA, one of the three components of the C1q molecule based on the hexamer of trimers composed of three distinct polypeptide chains, is considered to be the first component in the classical pathway and plays a crucial role in the innate immune response, defence against invading pathogens and activation of complement by binding to immune complexes [ 32 , 33 ]. CFD, a member of the trypsin family, activates the alternative pathway by cleaving C3b-bound factor B and is involved in innate and adaptive defences against pathogen infection [ 34 , 35 ].…”

“…The complement and coagulation cascades, which function as major proteolytic cascades in blood serum, are reported to be composed of more than 35 soluble plasma proteins, and recent evidence suggests that the complement and coagulation cascades mediate the response to acute injury by limiting bleeding and pathogen invasion and facilitating wound healing [ 33 , 40 – 42 ]. Additionally, several studies have shown that the complement and coagulation cascades are not merely processes reactive to inflammation, immunity and haemostasis but also rather critical determinants of liver disease pathogenesis [ 34 , 37 ].…”

Serum Proteomic Profiling in Patients with Advanced Schistosoma Japonicum-Induced Hepatic Fibrosis

“…The expression of C1QA was signi cantly upregulated in the serum samples of SHF-F4 patients compared to those of healthy control individuals and SHF-F2 patients. C1QA is the main recognition protein in the classical complement pathway and plays key roles in the innate immune response and defence against dangerous factors in the presence of injured cells, accumulating debris, or foreign materials [32,33]. On the other hand, it is associated with several modulatory processes, including pathogen clearance, angiogenesis, autoimmunity, apoptosis, tolerance, chemotaxis and homeostasis.…”

“…5), the proteins complement C1q subcomponent subunit A (C1QA, 1.82-fold) and complement factor D (CFD, 2.51-fold) were differentially expressed in the SHF-F4 and SHF-F2 groups of schistosomiasis patients. C1QA, one of the three components of the C1q molecule based on the hexamer of trimers composed of three distinct polypeptide chains, is considered the rst component in the classical pathway and plays a crucial role in the innate immune response, defence against invading pathogens and activation of complement by binding to immune complexes [32,33]. CFD, a member of the trypsin family, activates the alternative pathway by cleaving C3b-bound factor B and is involved in innate and adaptive defences against pathogen infection [34,35].…”

From Classical to Unconventional: The Immune Receptors Facilitating Platelet Responses to Infection and Inflammation

“…gC1qR interacts with the C-terminal globular domain on C1q (gC1q) [ 113 ]. Both domains may participate in platelet activation as binding of C1q to platelets has shown to induce platelet aggregation and P-selectin expression [ 117 , 118 ].…”