Faculty Collaboration Database

Thrombosis and inflammation as multicellular processes: significance of cell-cell interactions. Thromb Haemost 1995 Jul;74(1):213-7

Date

07/01/1995

Pubmed ID

8578460

DOI

10.1055/s-0038-1642679

Scopus ID

2-s2.0-0029093011 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

Platelet activation as a result of vascular injury provokes endothelial cells to respond in a manner which limits or reverses the occlusive consequences of platelet accumulation. If the agonistic forces are strong, platelet accumulation is irreversible. In vitro data from our laboratory have repeatedly demonstrated that platelets become unresponsive to all agonists when in proximity to endothelial cells. This unresponsiveness is due to at least three separate endothelial "thromboregulatory" systems: eicosanoids, endothelium-derived relaxing factor (EDRF/NO), and most importantly an endothelial cell ecto-nucleotidase which metabolizes released platelet adenosine diphosphate (ADP) with consequent restoration of platelets to the resting state. This nucleotidase is operative in the complete absence of EDRF/NO and eicosanoids, indicating that the latter two are dispensable thromboregulators. We have solubilized the human endothelial cell ectoADPase, as well as that from placental tissue. Candidate proteins from a purified ADPase fraction are now being studied in further detail. An understanding of the molecular biology of the ADPase gene may lead to development of therapeutic agents such as soluble forms of the enzyme as well as approaches toward up-regulation of ectoADPase activity. This could result in "early thromboregulation", i.e. prevention and/or reversal of platelet accumulation at sites of vascular damage via immediate metabolic removal of the prime platelet agonist-ADP.

Author List

Marcus AJ, Safier LB, Broekman MJ, Islam N, Fliessbach JH, Hajjar KA, Kaminski WE, Jendraschak E, Silverstein RL, von Schacky C

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Diphosphate
Apyrase
Aspirin
Blood Platelets
Cyclooxygenase Inhibitors
Eicosanoids
Endothelium, Vascular
HSP70 Heat-Shock Proteins
Humans
Inflammation
Nitric Oxide
Platelet Activation
Thrombosis