Erythroid burst-promoting activity produced by interleukin-1-stimulated endothelial cells is granulocyte-macrophage colony-stimulating factor.
Interleukin-1 (IL-1) induces cultured human umbilical vein endothelial cells to elaborate heterogeneous hematopoietic growth factors, including granulocyte-macrophage and granulocyte colony-stimulating factors (GM-CSF and G-CSF, respectively). Because erythroid burst-promoting activity (BPA) is also elaborated by endothelial cells exposed to IL-1, we sought to determine whether the BPA released by IL-1-induced endothelial cells simply reflects the known erythropoietic activity of GM-CSF or whether other uncharacterized factors might be involved. Media conditioned by multiply passaged endothelial cells cultured for three days with recombinant IL-1 alpha (ECMIL-1) stimulated erythroid burst and GM colony formation in cultures of human nonadherent T-lymphocyte-depleted marrow mononuclear cells. Pretreatment with an anti-GM-CSF antiserum neutralized all the BPA and 56% of the GM colony-stimulating activity (GM-CSA) in ECMIL-1. The antiserum used in these studies did not inhibit IL-3 or G-CSF activity and did not inhibit ECMIL-1-induced murine GM colony growth (a measure of human G-CSF). To examine whether GM-CSF induces BPA release by accessory cells, media conditioned by marrow cells cultured for three days with GM-CSF were tested in the colony growth assays. Pretreatment with anti-GM-CSF antiserum completely neutralized the BPA and GM-CSA of the marrow cell-conditioned medium. We conclude that GM-CSF is the BPA elaborated by IL-1-induced endothelial cells. The in vitro erythropoietic activity of GM-CSF is not dependent on induced BPA release by accessory cells and therefore likely results from a direct effect of GM-CSF on progenitor cells.
D000328:Adult; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D003470:Culture Media; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004920:Erythropoiesis / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D007375:Interleukin-1; D008222:Lymphokines / Q000096:biosynthesis* / Q000502:physiology; D019714:Tissue Inhibitor of Metalloproteinases
D003115:Colony-Stimulating Factors; D003470:Culture Media; D006131:Growth Inhibitors; D006133:Growth Substances; D007106:Immune Sera; D007375:Interleukin-1; D008222:Lymphokines; D019714:Tissue Inhibitor of Metalloproteinases; D016178:Granulocyte-Macrophage Colony-Stimulating Factor