Interleukin 1 stimulates endothelial cells to release multilineage human colony-stimulating activity

G. M. Segal, E. McCall, T. Stueve, G. C. Bagby

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    Abstract

    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 1β (rIL 1) and media conditioned by monocytes (MCM), endothelial cells (ECM), and endothelial cells cultured for 3 days in 50% MCM (ECM(M)) or rIL 1 (ECM(rIL 1)) were added to marrow mononuclear cells cultured in methylcellulose. ECM(M) and ECM(rIL 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 ECM(M) and ECM(rIL 1) concentrations in culture of 1 to 5%, was partially masked by lineage-specific inhibitors of Meg colony growth. When ECM(M) was analyzed by gel filtration chromatography, the megakaryocytopoietic inhibitory activity eluted in the high M(r) fractions (>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.

    Original languageEnglish (US)
    Pages (from-to)1772-1778
    Number of pages7
    JournalJournal of Immunology
    Volume138
    Issue number6
    StatePublished - Jan 1 1987

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    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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