Inhibition of human endothelial cell growth by human monocytes in coculture

Previous studies conducted in different experimental models have shown that human monocytes (Mo) possess both stimulating and inhibiting factors for endothelial cell growth. Since Mo are frequently found in the vicinity of endothelial cells, we examined the direct effect of human peripheral blood Mo on the proliferation of human umbilical vein endothelial cells (HEC) in in vitro culture systems. Mo obtained either by counter centrifugation elutriation or by selective adhesion on gelatin-autologous plasma or purified fibronectin coated plastic surfaces inhibited HEC growth as determined by HEC count or 3H-methyl thymidine incorporation. This growth inhibitory effect was dependent on the number of monocytes: 50% inhibition of 3H-thymidine uptake by HEC was achieved for a Mo-EC ratio of 1:4. Mo isolation by selective adhesion on gelatin-plasma resulted in a significantly higher inhibitory effect (p less than 0.02) than that observed with Mo isolated on fibronectin coated surfaces or by elutriation techniques, suggesting a possible stimulation of Mo by contact with gelatin-plasma. Endothelial cell growth factor plus heparin did not reverse this inhibition of HEC growth. Results obtained in diffusion chamber and coculture systems showed that soluble products of Mo origin can inhibit HEC proliferation but the inhibition was greater when Mo and HEC were in contact. The effect was not due to cytotoxicity as evaluated by cell counting and 51Chromium release from HEC. These in vitro results suggest that normal monocytes could exert a regulatory role on the proliferation of endothelial cells.