INHIBITION OF ENDOTHELIAL CELL PROLIFERATION BY NORMAL HUMAN MONOCYTES

Human peripheral blood monocytes and macrophages possess factors which are capable of inhibiting or stimulating endothelial cell proliferation. We have further explored if such activity is due to cytotoxic effects of monocytes. Normal mononuclear cells were isolated first by density gradient. Monocytes were then purified by three different techniques: 1) counter centrifugation elutriation (CCE) (Beckman) 2) selective adhesion to gelatin-plasma (GPI) 3) selective adhesion to fibronectin (Fn). Cytotoxicity was estimated by counting the release of 51cr used to label the human umbilical vein endothelial cells (HUVE) prior to the addition of monocytes. Whilst [3H] thymidine incorporation by HUVE permitted us to measure the effect of monocytes on the growth of the endothelial cells. Monocytes were incubated with HUVE (12×103) for 24 to 36h at various concentrations '(1.5-12×103). No cytotoxic effect could be demonstrated but an inhibition of [3h] thymidine uptake was observed and was dependent upon monocytes concentration. Monocytes isolated on GP1 exhibited a significantly higher inhibitory effect (p<0.05) compared to those purified on Fn or by CCE.(GP1: 85±6%, Fn:58±6%, CCE:67±5%). These results indicated t*hat normal monocytes can inhibit endothelial cell proliferation. This activity appeared to be higher when monocytes were isolated on GP1 which suggest that the adhesion on this surface could stimulate monocytes not only by its fibronectin receptor. This inhibitory activity of monocyte on endothelial cells proliferation could be different in patients with vascular disorders.