Circulation, Vol 72, 718-727, Copyright © 1985 by American Heart Association
GA Zimmerman, TM McIntyre and SM Prescott
Primary cultures of confluent endothelial cells derived from human
umbilical veins produce platelet-activating factor (PAF) (1-alkyl-2-
acetyl-sn-glycero-3-phosphocholine) when stimulated with appropriate
agonists. Highly purified human thrombin and calcium ionophore A23187
stimulate the incorporation of [3H] acetate into a lipid product that has
been identified as PAF by its behavior in thin-layer chromatographic and
high-performance liquid chromatographic systems, the presence of
characteristic biologic activity, and appropriate response to
phospholipases. A number of other humoral mediators, examined because they
directly influence the activity of vascular cells or because they may
mediate endothelial injury, do not stimulate PAF production by endothelial
cells. This indicates that the synthesis of PAF by cultured human
endothelial cells is a response to specific agonists and is not an
unregulated event that occurs as a result of nonspecific cellular
perturbation. The PAF produced by thrombin-treated endothelial cells is a
potent stimulus for platelet activation, as assayed by the aggregation of
human platelets in autologous plasma. The production of PAF by endothelial
monolayers is attenuated by prostacyclin, another product of stimulated
endothelial cells. Conversely, PAF production is enhanced by treatment of
the endothelial cells with indomethacin, an inhibitor of prostacyclin
synthesis from arachidonic acid, indicating that endogenously generated
prostacyclin may modulate PAF synthesis. The potential to synthesize PAF, a
unique lipid autocoid that stimulates the activation of both platelets and
polymorphonuclear leukocytes, suggests that endothelial cells can directly
influence the activity of these circulating effector cells. This biologic
potential may be important in the interaction of the endothelium with
circulating blood cells in physiologic conditions and in syndromes of
vascular injury.
ARTICLES
Production of platelet-activating factor by human vascular endothelial cells: evidence for a requirement for specific agonists and modulation by prostacyclin
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