Granulocyte colony-stimulating factor receptors on granulocytes are down-regulated after endotoxin administration to healthy humans.
Granulocyte colony-stimulating factor (G-CSF) is considered an important mediator of host defense against infection, and recombinant G-CSF is administered to patients with various infections. G-CSF binds to a specific receptor that is expressed on granulocytes and monocytes. To obtain insight about the regulation of the G-CSF receptor after an acute infectious challenge, 8 healthy subjects received an intravenous injection of lipopolysaccharide (LPS; 4 ng/kg), and receptor expression was determined on blood leukocytes by fluorescence-activated cell sorter analysis, both by measurement of saturation binding of recombinant G-CSF and by use of an anti-G-CSF-receptor antibody. LPS induced a transient decrease in granulocyte, but not monocyte, G-CSF-receptor expression. In whole blood in vitro, not only LPS but also gram-positive stimuli and proinflammatory cytokines were capable of down-modulating the G-CSF receptor on granulocytes. Bacterial antigens down-regulate the G-CSF receptor at the surface of granulocytes, which may impair neutrophil functions important for antibacterial host defense.
Dekkers
P E
PE
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Juffermans
N P
NP
Hove
T t
Tt
de Jonge
E
E
van Deventer
S J
SJ
van Der Poll
T
T
D000328:Adult; D006098:Granulocytes / Q000737:chemistry*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis*; D013997:Time Factors
D008070:Lipopolysaccharides; D016188:Receptors, Granulocyte Colony-Stimulating Factor