Murine macrophage P2X7 receptors support rapid prothrombotic responses

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 Ca(2+)-depen...

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Bibliographic Details
Published in:Cellular signalling 2007-04, Vol.19 (4), p.855-866
Main Authors: Moore, Samantha F, MacKenzie, Amanda B
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - pharmacology
Animals
Annexin A5 - metabolism
Biological Transport - drug effects
Calcium - metabolism
Cattle
Cell Line
Cell Survival - drug effects
Cytoplasmic Vesicles - drug effects
Cytoplasmic Vesicles - metabolism
Ethidium - metabolism
Humans
L-Lactate Dehydrogenase - secretion
Macrophages - cytology
Macrophages - metabolism
Macrophages - secretion
Macrophages - ultrastructure
Mice
Phosphatidylserines - metabolism
Protein Binding - drug effects
Prothrombin - metabolism
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2X7
Thromboplastin - metabolism
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Summary: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 Ca(2+)-dependent formation and release of PS-rich microvesicles that enhance the assembly of the prothrombinase complex and subsequent formation of thrombin. Incubation with P2X(7) 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 P2X(7) receptor can also support and propagate rapid increases in thrombin formation.
ISSN:0898-6568
DOI:10.1016/j.cellsig.2006.10.010