Endothelial cells potentiate phagocytic killing by macrophages via platelet-activating factor release

The immunomodulatory function of endothelial cells (EC) includes the initia tion of leukocyte margination, diapedesis, and activation through the upreg ulation of various cell surface-associated molecules. However, the effect t hat EC have on the phagocytic function of neighboring monocytes and macroph ages is less well described. To address this issue, microvascular EC were c ocultured with murine peritoneal macrophages, first in direct contact, then in a:noncontact coculture system, and macrophage phagocytosis and phagocyt ic killing were assessed. The presence of increasing concentrations of EC r esulted in a dose-dependent increase in,macrophage phagocytic killing. This stimulatory effect was: inhibited in a dose-dependent manner by the pretre atment of macrophage/EC cocultures with WEB-2086 or CV-6209, specific plate let-activating factor (PAF)-receptor antagonists, but not by anti-tumor nec rosis factor-alpha, anti-interleukin (IL)-1 alpha, or anti-IL-1 beta. Furth ermore, the effect was reproduced in the absence of EC by the exogenous adm inistration of nanomolar concentrations of PAF. Microvascular EC potentiate macrophage phagocytic killing via the release of a soluble signal; PAF app ears to be an important component of that signal.