Platelet-RBC interaction mediated by FasL/FasR induces procoagulant activity important for thrombosis
| العنوان: | Platelet-RBC interaction mediated by FasL/FasR induces procoagulant activity important for thrombosis |
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| المؤلفون: | Martin Schaller, Nina Sarah Gowert, Christoph Klatt, Lena Pfaff, Hubert Schelzig, Hadi Al-Hasani, Irena Krüger, Steffen Massberg, Martina Spelleken, Jürgen Schrader, Kerstin Jurk, Saskia Zey, Kim-Jürgen Krott, Margitta Elvers, Alexander Oberhuber, Malte Kelm, Konstantin Stark, Wiebke Lückstädt |
| المصدر: | Journal of Clinical Investigation. 128:3906-3925 |
| بيانات النشر: | American Society for Clinical Investigation, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Blood Platelets, 0301 basic medicine, Erythrocytes, Fas Ligand Protein, Population, 030204 cardiovascular system & hematology, Inferior vena cava, Fas ligand, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, medicine, Animals, Humans, Platelet, Platelet activation, Thrombus, education, Hemostasis, education.field_of_study, Chemistry, Thrombosis, hemic and immune systems, Receptors, Death Domain, General Medicine, Phosphatidylserine, medicine.disease, 030104 developmental biology, medicine.vein, cardiovascular system, Cancer research, Research Article, circulatory and respiratory physiology |
| الوصف: | Red blood cells (RBCs) influence rheology, and release ADP, ATP, and nitric oxide, suggesting a role for RBCs in hemostasis and thrombosis. Here, we provide evidence for a significant contribution of RBCs to thrombus formation. Anemic mice showed enhanced occlusion times upon injury of the carotid artery. A small population of RBCs was located to platelet thrombi and enhanced platelet activation by a direct cell contact via the FasL/FasR (CD95) pathway known to induce apoptosis. Activation of platelets in the presence of RBCs led to platelet FasL exposure that activated FasR on RBCs responsible for externalization of phosphatidylserine (PS) on the RBC membrane. Inhibition or genetic deletion of either FasL or FasR resulted in reduced PS exposure of RBCs and platelets, decreased thrombin generation, and reduced thrombus formation in vitro and protection against arterial thrombosis in vivo. Direct cell contacts between platelets and RBCs via FasL/FasR were shown after ligation of the inferior vena cava (IVC) and in surgical specimens of patients after thrombectomy. In a flow restriction model of the IVC, reduced thrombus formation was observed in FasL–/– mice. Taken together, our data reveal a significant contribution of RBCs to thrombosis by the FasL/FasR pathway. |
| تدمد: | 1558-8238 0021-9738 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6feaf93a2349fea3f4b6901b7b4814d7Test https://doi.org/10.1172/jci92077Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6feaf93a2349fea3f4b6901b7b4814d7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15588238 00219738 |
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