Modulation of receptors for the colony-stimulating factor, CSF-1, by bacterial lipopolysaccharide and CSF-1.
The ability of the mononuclear phagocyte-specific colony-stimulating factor, CSF-1, to down-regulate its receptor on peritoneal exudate macrophages (PEM) was examined. Because of the essentially irreversible binding of CSF-1 to its receptor at 2 degrees C, unoccupied cell surface receptors could be measured by rapidly cooling PEM to 2 degrees C and determining the amount of 125I-CSF-1 bound at this temperature. On incubation with 125I-CSF-1 at 37 degrees C more receptors were lost than could be accounted for by 125I-CSF-1 binding. This receptor loss, apparently caused by CSF-1 itself, was shown to be due in large part to the presence of contaminating lipopolysaccharide (LPS), which at 10 ng/ml was by itself able to cause complete loss of the CSF-1 receptors. LPS also induced loss of the insulin receptor by PEM. LPS did not cause apparent CSF-1 receptor loss by binding to the receptor or by stimulating the release of CSF-1 or substances which compete for the binding of 125I-CSF-1 to the receptor. However, LPS did stimulate release of factors by LPS responsive (C3H/HeN) PEM which caused CSF-1 receptor loss by LPS non-responsive (C3H/HeJ) PEM. In the absence of LPS induced effects, incubation of 125I-CSF-1 with PEM at 37 degrees C resulted in down-regulation of the CSF-1 receptors. The number of CSF-1 receptor sites down-regulated corresponded to the number of CSF-1 molecules that were cell-associated plus the number that were intracellularly degraded and released.
D000818:Animals; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects*; D016184:Receptors, Colony-Stimulating Factor
D003115:Colony-Stimulating Factors; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D011972:Receptor, Insulin