Lipopolysaccharide inhibits the binding of colony-stimulating factor (CSF-1) to murine peritoneal exudate macrophages.
These studies demonstrate the potent effect of bacterial endotoxin (LPS) on the inhibition of iodinated colony-stimulating factor- (125I-CSF-1) binding by murine peritoneal exudate macrophages (PEM) from C3H/An and C57BL/6 mice. As small an amount as 0.1 ng/ml LPS is sufficient to cause a significant inhibitory effect; this effect is temperature-, time- and concentration-dependent. LPS, however, causes minimal or no inhibition of 125I-CSF-1-binding by PEM from LPS-resistant C3H/HeJ mice. Inhibition of 125I-CSF-1-binding does not appear to be a result of a direct occupancy by LPS of CSF-1 receptors present on the cell membrane and is most likely due to a progressive loss of available CSF-1-binding sites. The effect can be neutralized by the addition of the antibiotic polymyxin B, which binds to the lipid A portion of LPS. The action of LPS on PEM is transient; treated cells recover their 125I-CSF-1-binding activity whether or not LPS is later removed. The restoration of 125I-CSF-1-binding activity can be blocked completely by the addition of cyclohexamide. These findings suggest the rapid, LPS-induced disappearance of CSF-1 receptors from the cell surface may be related to the activation of macrophages by LPS.
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D001667:Binding, Competitive / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000145:classification / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011112:Polymyxin B / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000187:drug effects; D016184:Receptors, Colony-Stimulating Factor; D013696:Temperature
D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D003513:Cycloheximide; D011112:Polymyxin B