Abstract
Although erythrocytes have been suggested to play a role in blood clotting, mediated through phosphatidylserine (PS) exposure and/or PS-bearing microvesicle generation, an endogenous substance that triggers the membrane alterations leading to a procoagulant activity in erythrocytes has not been reported. We now demonstrated that lysophosphatidic acid (LPA), an important lipid mediator in various pathophysiological processes, induces PS exposure and procoagulant microvesicle generation in erythrocytes, which represent a biological significance resulting in induction of thrombogenic activity. In human erythrocytes, LPA treatment resulted in PS exposure on remnant cells and PS-bearing microvesicle generation in a concentration-dependent manner. Consistent with the microvesicle generation, scanning electron microscopic study revealed that LPA treatment induced surface changes, alteration of normal discocytic shape into echinocytes followed by spherocytes. Surprisingly, chelation of intracellular calcium did not affect LPA-induced PS exposure and microvesicle generation. On the other hand, protein kinase C (PKC) inhibitors significantly reduced PS exposure and microvesicle generation induced by LPA, reflecting the role of calcium-independent PKC. Activation of PKC was confirmed by Western blot analysis showing translocation of calcium-independent isoform, PKCzeta, to erythrocyte membrane. The activity of flippase, which is important in the maintenance of membrane asymmetry, was also inhibited by LPA. Furthermore, LPA-exposed erythrocytes actually potentiated the thrombin generation as determined by prothrombinase assay and accelerated the coagulation process initiated by recombinant human tissue factor in plasma. The adherence of erythrocytes to endothelial cells, another important feature of thrombogenic process, was also stimulated by LPA treatment. These results suggested that LPA-exposed erythrocytes could make an important contribution to thrombosis mediated through PS exposure and procoagulant microvesicle generation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
More From: Arteriosclerosis, Thrombosis, and Vascular Biology
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.