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 fluorescenceactivated cell sorter analysis, both by measurement of saturation binding of recombinant GCSF 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 downmodulating the G-CSF receptor on granulocytes. Bacterial antigens down-regulate the GCSF receptor at the surface of granulocytes, which may impair neutrophil functions important for antibacterial host defense.