Activation of Neutrophils and Platelets by Various Mediators of Acute Inflammation : Influence of Vascular Endothelial Cells and Various Xanthine Derivatives

AbstractWith the aid of a novel filtration system for blood, into which a lining of confluent endothelial cells can be incorporated, cellular interactions can now be investigated in streaming whole blood under conditions largely approximating those in vivo. Reductions in filtration rate are elicited by FMLP, ADP and PAF in a concentration-dependent manner, due to the activation and aggregation of neutrophils (PMN) and platelets. These effects can be antagonized by exogenously applied adenosine, PGE1 and PGE2 in physiological concentrations. Cultured vascular endothelial cells also inhibit the actions of the above listed mediators of inflammation on these blood cells, presumably by releasing the corresponding endogenously produced prostaglandins and adenosine into the streaming blood. In the physiological state, this inhibitory effect of the endothelium probably suppresses the manifestation of inflammatory processes in the intact parts of the vascular system downstream of the inflammatory site. Interestingly, various xanthine derivatives, such as pentoxifylline, are capable of enhancing this endothelial function already at concentrations within their therapeutic range.