Lipopolysaccharide-induced CD11B-mediated neutrophil-endothelial adhesion is not required for polymorphonuclear cell priming.
Previous work has implicated both neutrophil-endothelial cell (PMN-EC) adhesion and PMN priming (enhanced superoxide production following activation) in the development of postinjury adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). CD11B, a member of the integrin family of PMN surface receptors, has been alleged to have a prominent role in these inflammatory PMN-EC processes. The purpose of the present study was to test the hypothesis that CD11B-mediated PMN-EC adhesion is necessary for endotoxin (LPS)-induced PMN priming. Human neutrophils, isolated by Percoll gradient centrifugation, were exposed to LPS (100 ng/mL). At fixed times over 120 minutes (a) superoxide following fMLP activation (i.e., priming), (b) PMN-EC adhesion, and (c) expression of CD11B were assayed. Superoxide production was measured by cytochrome c reduction, PMN-EC adhesion with indium-labelled PMN adherence to human umbilical vein endothelial cell (HUVEC) monolayer cultures, and CD11B expression with fluorescent labelled anti-CD11B (60.1) antibodies. The PMN-EC adhesion was biphasic, with an early maximum at 15 minutes followed by a nadir at 60 minutes and secondary rise through 120 minutes of LPS exposure. CD11B expression changed dramatically in temporal association with early PMN-EC adhesion, but the secondary increase in adhesion was associated with only a mild rise in CD11B expression. PMN priming increased after a latency of 15 minutes to a maximum of 800 nmol/10(6) cells/min after 60 minutes of LPS exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
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Department of Surgery, Denver General Hospital, CO 80204-4507.
Moore
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Carl
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D002448:Cell Adhesion / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D007205:Indium Radioisotopes; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D013481:Superoxides / Q000032:analysis; D014471:Umbilical Veins
D007205:Indium Radioisotopes; D008070:Lipopolysaccharides; D016177:Macrophage-1 Antigen; D013481:Superoxides