The Production of Platelet-Activating Factor by Cultured Human Endothelial Cells: Regulation and Function

Abstract

Under usual physiological conditions, the vascular endothelium must present a nonthrombogenic surface to the blood to prevent diffuse thrombosis (reviewed by Gingrich and Hoak, 1979). The mechanism(s) for this characteristic of endothelial cells has not been elucidated and is the subject of intense investigation. However, there are other circumstances in which the rapid, specific attraction of blood cells to the endothelium is essential to maintain vascular integrity and to respond to extra-vascular events. In the first instance, damage to the endothelium must be repaired to prevent hemorrhage and exudation. Clinical observations and studies of organ perfusion in vitro (Gimbrone et al., 1969; Kitchens and Weiss, 1975) have provided compelling evidence that platelets are critical in maintaining vascular integrity under basal conditions. These observations suggest that platelets interact with the endothelial cells continuously in vivo. With respect to the second situation, circulating leukocytes bind to the end othelium (margination) in response to appropriate soluble stimuli (reviewed by Harlan, 1985) and emigrate from the vasculature to sites of inflammation such as infection. The latter response must involve a specific targeting mechanism, which presumably would include the endothelium, to attract leukocytes to the appropriate sites. Accordingly, the recently described production of procoagulant activities [e.g., coagulation factors (Rodgers and Shuman, 1983) and glycoproteins similar to platelet adhesive molecules (Fitzgerald et al., 1985)] and chemotactic factors [e.g., platelet-derived growth factor (DiCorleto and Bowen-Pope, 1983)] by endothelium may be viewed as homeostatic responses.