INTERACTIONS OF PLATELETS AND LEUKOCYTES WITH VASCULAR ENDOTHELIUM: In Vitro STUDIES*

Our studies suggest that the interactions of blood cells with cultured endothelial monolayers mimic in vivo phenomena, thus providing potentially useful in vitro experimental models. For example, normal endothelial cells in culture show little tendency to react with platelets, similar to their behavior in vivo. Production of anti-aggregatory prostaglandins, such as prostacyclin, by cultured endothelial cells does not appear to be necessary for their non-thrombogenicity. Significant changes in platelet reactivity can be observed when endothelial cells are altered by certain stimuli. Analogous alterations in vivo might constitute a form of endothelial dysfunction relevant to thrombosis and atherosclerosis. In contrast to platelets, PMN leukocytes appear to show a preferential adherence to cultured endothelial monolayers. As our data indicate, this basal adhesion, which is observed in the absence of exogenous chemotactic agents or other stimuli, is neither dependent upon endogenous cyclooxygenase derivatives of arachidonate, nor inhibited by exogenous prostacyclin. However, certain anti-inflammatory drugs and other agents, that can interfere with the metabolism of arachidonate via lipoxygenase pathways, do significantly reduce basal PMN leukocyte-endothelial interactions. Further definition of the cellular and biochemical sites of action of these compounds may provide new insights into the mechanisms of the inflammatory response. Finally, given the vast repertoire of biologically active substances that platelets and leukocytes can secrete or generate, the regulation of blood cell interaction with endothelium may represent a key locus for pharmacological intervention in the treatment and prevention of vascular diseases.