In vitro studies of thromboresistance: the role of prostacyclin (PGI2) in platelet adhesion to cultured normal and virally transformed human vascular endothelial cells.
Circulating blood platelets normally do not adhere to, or aggregate on, the vascular endothelial lining. We have developed an in vitro model system to study the mechanisms of endothelial resistance to platelet adhesion, and to determine the role of prostacyclin (PGI2) in this process. This system combines scanning electron microscopy and measurement of bound (3H)-adenine-labeled platelets to examine platelet adhesion to primary cultures of human endothelial cells, which generate PGI2-like activity, and to virally transformed endothelial cells, which lack this activity. Under basal conditions primary cultures bound less than one platelet per cell (228 +/- 8 c.p.m. per 10(4) cells, mean +/- standard error of the mean). Inhibition of endothelial PGI2 production by 50 microM aspirin or 2.8 microM indomethacin did not result in a significant change in platelet adherence. Stimulating prostaglandin production with arachidonic acid, or adding exogenous PGI2 did not depress platelet adhesion below the basal levels observed with untreated cultures. In contrast ot primary cultures, transformed endothelium showed markedly increased platelet adherence (3,993 +/- 194 c.p.m. per 10(4), mean +/- standard error of the mean), in the form of single platelets and clusters of two to five nonaggregated platelets. Although exogenous PGI2 was effective in hibiting platelet adherence to these transformed cells, even pharmacologic doses (1 microgram. per ml.) did not depress adhesion to the basal levels associated with normal cells. These results suggest that endothelial properties essential to blood compatibility are altered by viral transformation, and further, that generation of PGI2 by normal endothelium is not the key factor which prevents platelet adherence to the intact vessel wall.
D001241:Aspirin / Q000494:pharmacology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004727:Endothelium / Q000502:physiology; D011464:Epoprostenol / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation; D011453:Prostaglandins / Q000502:physiology*; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D013539:Simian virus 40; D014680:Veins / Q000502:physiology*
D011453:Prostaglandins; D011465:Prostaglandins, Synthetic; D011464:Epoprostenol; D001241:Aspirin