Interleukin 1 stimulates endothelial cells to release multilineage human colony-stimulating activity.
Cultured human umbilical vein endothelial cells, when exposed to soluble products of peripheral blood monocytes, elaborate granulocyte-macrophage colony-stimulating activity (GM-CSA) and erythroid burst-promoting activity (BPA). We have performed studies to determine if the monokine IL 1 can stimulate endothelial cells to release hematopoietic growth factors and whether such factors can also support human megakaryocyte (Meg) and mixed-cell colony growth. Various concentrations of recombinant human IL 1 beta (rIL 1) and media conditioned by monocytes (MCM), endothelial cells (ECM), and endothelial cells cultured for 3 days in 50% MCM (ECMM) or rIL 1 (ECMrIL 1) were added to marrow mononuclear cells cultured in methylcellulose. ECMM and ECMrIL 1 stimulated, in a dose-dependent fashion, the growth of Meg, mixed-cell, and GM colonies and erythroid bursts. In contrast, ECM, MCM, and rIL 1 displayed little or no activity in the colony-forming assays. Preincubation with specific antisera to native human IL 1 or rIL 1 reduced by 75 to 100% the activity of MCM in stimulating endothelial cell release of BPA, GM-CSA, Meg-CSA, and mixed-cell CSA. Meg-CSA, although readily detectable at ECMM and ECMrIL 1 concentrations in culture of 1 to 5%, was partially masked by lineage-specific inhibitors of Meg colony growth. When ECMM was analyzed by gel filtration chromatography, the megakaryocytopoietic inhibitory activity eluted in the high Mr fractions (greater than 75 kD). Meg-CSA co-eluted with GM-CSA and BPA in a single peak of 30 kD. We conclude that endothelial cells, in response to IL 1, produce one or more growth factors that probably act on multiple classes of progenitor cells.
D002478:Cells, Cultured; D004727:Endothelium / Q000378:metabolism*; D006133:Growth Substances / Q000378:metabolism*; D006410:Hematopoiesis; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000378:metabolism*; D008533:Megakaryocytes / Q000166:cytology; D008970:Molecular Weight; D012636:Secretory Rate / Q000187:drug effects
D006133:Growth Substances; D007375:Interleukin-1; D007377:Interleukin-3