title: Hierarchical down-modulation of hemopoietic growth factor receptors.
abstract: Granulocytes and macrophages can be produced in vitro when progenitor cells from mouse bone marrow are stimulated by any of four distinct colony stimulating factors, Multi-CSF (IL-3), GM-CSF, G-CSF, and M-CSF (CSF-1). At 0 degrees C the four CSFs do not cross-compete for binding to bone marrow cells, indicating that each has a specific cell surface receptor. However, at 21 degrees C or 37 degrees C, Multi-CSF inhibits binding of the other three CSFs and GM-CSF inhibits binding of G-CSF and M-CSF. Rather than competing directly for receptor binding, the binding of Multi-CSF, GM-CSF, or G-CSF to their own receptor induces the down-modulation (and thus activation) of other CSF receptors at 37 degrees C. The pattern and potency of down-modulation activity exhibited by each type of CSF parallels the pattern and potency of its biological activity. We propose a model in which the biological interactions of the four CSFs are explained by their ability to down-modulate and activate lineage-specific receptors.
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology* / Q000378:metabolism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000378:metabolism*; D016184:Receptors, Colony-Stimulating Factor; D013696:Temperature
chemical_list: D003115:Colony-Stimulating Factors; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor