Perflubron attenuates neutrophil adhesion to activated endothelial cells in vitro.
Infiltration of activated neutrophils into the lung appears to be a key element in the severe lung injury that develops in animal models of acute lung injury. Partial liquid ventilation with perflubron has been shown to ameliorate tissue damage compared with conventional mechanical ventilation in acute lung injury models. Pilot experiments indicated that indirect exposure to perflubron could modulate the degree to which subsequent neutrophil binding to endothelial cell monolayers was upregulated after lipopolysaccharide activation. Endothelial cell monolayers preexposed to perflubron showed >40% reductions in the surface steady-state levels of E-selectin and intercellular adhesion molecule-1 achieved after proinflammatory activation (P < 0.05), which correlated with a reduction in the real-time association constants measured by biosensor techniques. These results indicate that direct contact with the perflubron liquid phase is not necessary to attenuate inflammatory responses. Rather, diffusion of perflubron from the alveolar space into the adjacent pulmonary vascular endothelial layer may modulate neutrophil adhesion and thereby reduce the rate of infiltration of activated neutrophils into the injured lung.
Woods
C M
CM
Department of Biological Research, Alliance Pharmaceutical Corporation, San Diego, California 92121, USA. cmw@allp.com
Neslund
G
G
Kornbrust
E
E
Flaim
S F
SF
D001802:Blood Substitutes / Q000493:pharmacokinetics*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004058:Diffusion; D019040:E-Selectin / Q000032:analysis / Q000378:metabolism; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005466:Fluorocarbons / Q000493:pharmacokinetics*; D006801:Humans; D006842:Hydrocarbons, Brominated; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects
D001802:Blood Substitutes; D019040:E-Selectin; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; C003072:perflubron