Inhibition of endotoxin-mediated activation of endothelial cells by a perfluorocarbon emulsion.
Endothelial cell (EC) activation plays a key role in the inflammatory response by promoting the margination of leukocytes in inflamed loci. Augmented leukocyte margination to activated EC is mediated by the increased display of leukocyte adhesion molecules on EC surface membranes. The biocompatibility of synthetic oxygen-transport fluids is intimately linked to EC function, since one of the first tissues encountered by such fluids is the vascular endothelium. We investigated the effect of one such agent, a phospholipid-based perfluorocarbon emulsion containing 90% w/v perflurooctyl bromide (perflubron, PFOB) on EC activation. Human umbilical vein EC (HUVEC) were activated by 5 U/ml interleukin-1 (IL-1), 20 U/ml tumor necrosis factor (TNF), or 50 ng/ml E coli endotoxin (LPS) in the presence or absence of up to 20%, w/v perflubron. HUVEC activation was monitored by the extent of up-regulation of expression of intercellular adhesion molecule-1 (ICAM) and endothelial-leukocyte adhesion molecule-1 (ELAM). Exposure of HUVEC to perflubron did not alter the up-regulation of ICAM or ELAM in response to IL-1 or TNF (n = 20). However, at 10% perflubron ICAM up-regulation in response to LPS was inhibited by 95 +/- 6% (n = 9; p less than .05). ELAM expression was similarly affected. The concentration of perflubron required to diminish LPS-induced up-regulation by 50% was 6.0 +/- 0.6% (n = 3). The inhibitory effect of 10% perflubron was overcome by greater than 1 ug/ml LPS (n = 3) and the inhibitory effect was attenuated by adding perflubron to the cultures after LPS.(ABSTRACT TRUNCATED AT 250 WORDS)
Lane
T
T
UCSD School of Medicine.
Smith
D
D
Wancewicz
E
E
Funk
R
R
D001802:Blood Substitutes / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D019040:E-Selectin; D004655:Emulsions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D005466:Fluorocarbons / Q000494:pharmacology*; D006801:Humans; D006842:Hydrocarbons, Brominated; D018799:Intercellular Adhesion Molecule-1; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity; D015854:Up-Regulation
D001802:Blood Substitutes; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D004655:Emulsions; D004731:Endotoxins; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; C003072:perflubron