ALTERATIONS IN HUMAN ENDOTHELIAL-CELL MORPHOLOGY, PROLIFERATION AND FUNCTION BY A MACROPHAGE-DERIVED FACTOR

Changes in endothelial cell (EC) morphology occur at sites of physiolo gical lymphocyte traffic and in areas of chronic inflammation. Previou s studies have shown that EC shape changes also occur in vitro followi ng exposure of EC monolayers to peripheral blood mononuclear cell (PBM C)-derived conditioned media (CM). In the present study, quantitative image analysis is used to define the cell of origin of the elongating factor(s), to examine changes in EC proliferation and function accompa nying PBMC-induced human EC elongation and to identify the active PBMC -derived products responsible for this elongation. By separating monon uclear cells into subpopulations (macrophages, B cells and T cells) an d adding conditioned media derived from these subpopulations to cultur ed ECs, the macrophage (M empty set) is shown to be the primary cell o f origin of the elongating factor(s). Furthermore, EC elongation is ac companied by both a dose-dependent decrease in cellular proliferation and an increase in prostacyclin production. These findings suggest tha t PBMC-induced changes in EC morphology may be associated with a shift from a proliferative state to a more secretory phase of the EC cycle. Finally, using recombinant factors it is shown that TNFalpha acting i n combination with IL-1 may be the active PBMC-derived products which contribute to EC elongation.