Erythropoietin causes down regulation of colony-stimulating factor (CSF-1) receptors on peritoneal exudate macrophages of the mouse.
We have shown that erythropoietin (epo), the primary regulator of erythrocyte formation, diminished the binding to peritoneal exudate macrophages (PEM) of the principal macrophage growth regulator, colony-stimulating factor (CSF-1). The effect of epo on 125I-CSF-1 binding was dose-dependent; at a concentration of 1-2 U of epo/ml (10(-10) M), CSF-1 binding was almost completely suppressed. Erythropoietin did not compete with CSF-1 for occupancy of the latter's receptors. The effect of epo on CSF-1 binding occurred at 37 degrees C but not at 2 degrees C, and during the continuous exposure of PEM to epo at 37 degrees C we found that CSF-1 binding reached a nadir at 1 h and recovered to pre-exposure levels in 7 h. Our novel results are consistent with the notion that specific receptors for epo exist on the cell surface of PEM and that binding of epo sets in motion a series of cellular events resulting in the internalization of CSF-1 receptors. Thus epo causes down regulation of CSF-1 receptors on PEM. We have previously shown that epo causes suppression of CSF-induced granulocyte-macrophage colony formation by mouse bone marrow cells. The results we present here provide a possible mechanism for these results.
D000818:Animals; D001681:Biological Assay; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D004921:Erythropoietin / Q000494:pharmacology*; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor
D003115:Colony-Stimulating Factors; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D004921:Erythropoietin