Upregulation of monocyte urokinase plasminogen activator receptor during human endotoxemia.
The receptor for urokinase-type plasminogen activator (uPAR) (CD87) plays an important role in leukocyte adhesion and migration. To assess the effect of endotoxin on cellular uPAR, uPAR expression was determined on leukocytes by fluorescence-activated cell sorter analysis in seven healthy subjects following intravenous injection of endotoxin (lot G; 4 ng/kg). Endotoxin induced a transient increase in uPAR expression on monocytes, reaching a 92% +/- 46% increase over baseline expression after 6 h (P < 0.05). Endotoxin did not influence uPAR expression on granulocytes, while uPAR remained undetectable on lymphocytes. Endotoxin also increased soluble uPAR levels in plasma (P < 0.05). Stimulation of human whole blood with endotoxin or gram-positive stimuli in vitro also resulted in an upregulation of monocyte uPAR expression. Although tumor necrosis factor alpha (TNF) upregulated monocyte uPAR expression, anti-TNF did not influence the endotoxin-induced increase in monocyte uPAR expression. These data suggest that infectious stimuli may influence monocyte function in vivo by enhancing the expression of uPAR.
Dekkers
P E
PE
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. P.E.Dekkers@AMC.UVA. NL
ten Hove
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T
te Velde
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van Deventer
S J
SJ
van Der Poll
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D000328:Adult; D001772:Blood Cell Count; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000139:chemically induced / Q000201:enzymology*; D004792:Enzyme Precursors / Q000097:blood*; D005434:Flow Cytometry; D006801:Humans; D007275:Injections, Intravenous; D007962:Leukocytes / Q000201:enzymology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000201:enzymology*; D011956:Receptors, Cell Surface / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation
D004792:Enzyme Precursors; D008070:Lipopolysaccharides; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014409:Tumor Necrosis Factor-alpha