Molecular communication between platelets and red blood cells

Qing Li, Purdue University

Abstract

We are studying the pathways of molecular communication between activated platelets and erythrocytes in order to identify the mechanism by which erythrocytes assist platelets in hemostatic plug formation. Signaling molecules produced during platelet activation (e.g. prostaglandin E2 (PGE2), ADP, AP4A and adenosine) were shown to reduce red cell osmotic fragility. This reduced fragility could, in most cases, be correlated with a decrease in red cell filterability through 3 μm filters. Examination of the mechanism responsible for the changes in osmotic fragility revealed the essential participation of erythrocyte protein kinase C. To further define this signaling pathway, subsequent studies were focused on the effect of PGE2 on red cell volume, ion transport and procoagulant activity. We show that 10−10 M PGE2 induces K + efflux in human red cells. The PGE2-stimulated K + loss was observed to be Ca++-dependent and inhibited by two Gardos channel inhibitors, charybdotoxin and clotrimazole. The loss of cellular K+ during PGE2 challenge resulted in cell dehydration and cell shrinkage which was probably responsible for the observed loss of filterability. To further characterize the mechanism by which activated platelets recruit erythrocytes in clot formation, we examined the effect of PGE2 treated-red cells on platelet activity. A 4∼5 fold enhancement in thrombin-induced platelet aggregation was observed when PGE2-treated red cells rather than untreated red cells were mixed with platelet rich plasma. Further, experiments which measured the “bleeding time” of blood passing through a small hole in an artificial vessel demonstrated that bleeding stopped 10 times faster when erythrocytes were pre-treated with PGE2 for 40 min than when they were left untreated, even though the same concentration of PGE2 itself did not affect platelet activity. Taken together, we propose that release of PGE2 and other signaling molecules such as ADP, AP4A, and adenosine by activated platelets constitutes part of a mechanism by which activated platelets may recruit adjacent erythrocytes to assist in clot formation.

Degree

Ph.D.

Advisors

Low, Purdue University.

Subject Area

Biochemistry|Molecular biology

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