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 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.