Effects of lipopolysaccharide on human endothelial cells in culture

Lipopolysaccharide (LPS) in concentrations up to 10 ug/ml did not induce detectable direct cytotoxicity in human umbilical vein, pulmonary artery, or pulmonary vein endothelial cells. By contrast, significant cytotoxicity was observed in bovine aortic endothelial cells exposed to LPS 0.01 ug/ml. Transmission electron microscopy of human umbilical vein cells exposed to LPS 10 ug/ml for 4 days revealed no significant ultrastructural abnormalities compared to control cells. Whereas human umbilical vein endothelial cell cytotoxicity was observed when neutrophils were stimulated with phorbol myristate acetate, LPS-stimulated neutrophils did not induce significant cytotoxicity even in the presence of fresh human serum as a complement source. Moreover, human umbilical vein endothelial cell factor VIII-antigen and fibronectin release, angiotensin-converting enzyme activity, and PGI₂ release were unaffected by a 24-hour exposure to LPS. Cytotoxicity, however, was produced when human umbilical vein endothelial cells were coincubated with LPS and cycloheximide. The proliferation of human umbilical vein endothelial cells was also inhibited after prolonged, continuous exposure to LPS 10 ug/ml. We conclude that LPS with or without complement or neutrophils does not induce significant human endothelial cell lysis or detachment. Moreover, brief exposure to LPS has minimal, direct effect on several functions of human endothelial cells in vitro.