The importance of phosphstidylserine continues to surface...and Ronin wants to kill clinical development and sell the development rights????
Different Potential of Extracellular Vesicles to Support Thrombin Generation: Contributions of Phosphatidylserine, Tissue Factor, and Cellular Origin.
Tripisciano C1, Weiss R1, Eichhorn T1, Spittler A2, Heuser T3, Fischer MB1,4, Weber V5,6.
Author information
1Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria.Core Facility Flow Cytometry & Surgical Research Laboratories, Medical University of Vienna, Lazarettgasse 14, 1090, Vienna, Austria.Electron Microscopy Facility, Vienna Biocenter Core Facilities, Dr.-Bohr-Gasse 3, 1030, Vienna, Austria.Center for Biomedical Technology, Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria.Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria. viktoria.weber@donau-uni.ac.at.Center for Biomedical Technology, Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Strasse 30, 3500, Krems, Austria. viktoria.weber@donau-uni.ac.at.
Abstract
Cells release diverse types of vesicles constitutively or in response to proliferation, injury, inflammation, or stress. Extracellular vesicles (EVs) are crucial in intercellular communication, and there is emerging evidence for their roles in inflammation, cancer, and thrombosis. We investigated the thrombogenicity of platelet-derived EVs, which constitute the majority of circulating EVs in human blood, and assessed the contributions of phosphatidylserine and tissue factor exposure on thrombin generation. Addition of platelet EVs to vesicle-free human plasma induced thrombin generation in a dose-dependent manner, which was efficiently inhibited by annexin V, but not by anti-tissue factor antibodies, indicating that it was primarily due to the exposure of phosphatidylserine on platelet EVs. Platelet EVs exhibited higher thrombogenicity than EVs from unstimulated monocytic THP-1 cells, but blockade of contact activation significantly reduced thrombin generation by platelet EVs. Stimulation of monocytic cells with lipopolysaccharide enhanced their thrombogenicity both in the presence and in the absence of contact activation, and thrombin generation was efficiently blocked by anti-tissue factor antibodies. Our study provides evidence that irrespective of their cellular origin, EVs support the propagation of coagulation via the exposure of phosphatidylserine, while the expression of functional tissue factor on EVs appears to be limited to pathological conditions.
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