Murine macrophage P2X7 receptors support rapid prothrombotic responses


Moore, S. F. and Mackenzie, A. B., 2007. Murine macrophage P2X7 receptors support rapid prothrombotic responses. Cellular Signalling, 19 (4), pp. 855-866.

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Non-apoptotic externalization of phosphatidylserine (PS) can act as a reactive surface for the efficient assembly of the prothrombinase complex leading to thrombin generation and coagulation. Here we show that extracellular ATP, acting at the macrophage P2X(7) receptor, drives the rapid Ca2+-dependent formation and release of PS-rich microvesicles that enhance the assembly of the prothrombinase complex and subsequent formation of thrombin. Incubation with P2X7 receptor antagonists (KN-62 and Brilliant Blue G) attenuates ATP induced prothrombotic responses. Consistent with the hypothesis that exposed PS enhances prothrombinase activity; pre-incubation with annexin V blocks the increase in thrombin formation. The rapid translocation of PS and formation of pro-thrombotic microvesicles occurs in the absence of cell lysis. These data demonstrate that the pro-inflammatory P2X7 receptor can also support and propagate rapid increases in thrombin formation.


Item Type Articles
CreatorsMoore, S. F.and Mackenzie, A. B.
DepartmentsFaculty of Science > Pharmacy & Pharmacology
ID Code19866


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