INVITRO STUDIES OF THROMBO-RESISTANCE - ROLE OF PROSTACYCLIN (PGI2) IN PLATELET-ADHESION TO CULTURED NORMAL AND VIRALLY TRANSFORMED HUMAN VASCULAR ENDOTHELIAL-CELLS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 42  (3) , 366-374
Abstract
Circulating blood platelets normally do not adhere to, or aggregate on, the vascular endothelial lining. An in vitro model system was developed 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 [SV 40] virally transformed endothelial cells, which lack this activity. Under basal conditions primary cultures bound less than 1 platelet/cell (228 .+-. 8 cpm/104 cells). Inhibition of endothelial PGI2 production by 50 .mu.M aspirin or 2.8 .mu.M 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 to primary cultures, transformed endothelium showed markedly increased platelet adherence (3993 .+-. 194 cpm/104) in the form of single platelets and clusters of 2-5 nonaggregated platelets. Although exogenous PGI2 was effective in inhibiting platelet adherence to these transformed cells, even pharmacologic doses (1 .mu.g/ml) did not depress adhesion to the basal levels associated with normal cells. Endothelial properties essential to blood compatibility are apparently altered by viral transformation, and generation of PGI2 by normal endothelium is apparently not the key factor which prevents platelet adherence to the intact vessel wall.