Bacterial lipopolysaccharides alter human endothelial cell morphology in vitro independent of cytokine secretion.
Lipopolysaccharides derived from six bacterial species were found to alter human endothelial cell morphology in vitro in a species-dependent and dose-dependent manner. Lipopolysaccharides derived from Salmonella enteritidis (SeLPS) induced the strongest response, whereas lipopolysaccharides from Vibrio cholerae produced no effect. Cell-shape changes induced by SeLPS (10 micrograms/ml) were noticeable by 24 hours and reached a maximum by 72 hours, thus paralleling the effects produced by the recombinant cytokines interferon gamma (IFN-gamma) (10(3) U/ml), tumor necrosis factor (10(2) U/ml), and interleukin-1 (5 to 10 U/ml). Pretreatment of human endothelial cells with IFN-gamma (10(3) U/ml) for 24 hours induced an accelerated morphologic response to subsequent SeLPS (10 micrograms/ml) stimulation and vice versa, suggesting independent pathways of action. Simultaneous treatment of human endothelial cells with SeLPS and IFN-gamma produced a more rapid onset of morphologic changes and a stronger overall effect. Culture medium containing polymyxin B inhibited cell-shape changes induced by lipopolysaccharides but not those induced by the cytokines. Conditioned medium generated over a 12-hour period following a 24-hour SeLPS/IFN-gamma stimulation did not contain measurable cytokine antigens, nor did it induce biologic responses associated with interleukin-1, IFN-gamma, and tumor necrosis factor alpha. The results indicate that lipopolysaccharides act directly on endothelial cells as well as synergistically with IFN-gamma to alter cell morphology and may, therefore, contribute to the vascular pathology of gram-negative infections.
Seifert
P S
PS
Unité d'Immunopathologie and INSERM U28, Hôpital Broussais, Paris, France.
Haeffner-Cavaillon
N
N
Appay
M D
MD
Kazatchkine
M D
MD
D001427:Bacterial Toxins / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D004731:Endotoxins / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000472:pathogenicity; D006098:Granulocytes / Q000166:cytology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008070:Lipopolysaccharides; D008854:Microscopy, Electron; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001427:Bacterial Toxins; D004731:Endotoxins; D015395:Histocompatibility Antigens Class I; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma