Faculty Research 1990 - 1999

Title

Synergistic interaction of bacterial lipopolysaccharide and the monocyte-macrophage colony-stimulating factor: potential quantitative and qualitative changes in macrophage-produced cytokine bioactivity.

Document Type

Article

Publication Date

1992

Keywords

Cells-Cultured, Comparative-Study, Cytokines: ge, ph, me, Drug-Synergism, Gene-Expression: de, ph, Interleukin-1: ge, ph, me, Interleukin-6: ge, ph, me, Lipopolysaccharides: ph, Macrophage-Colony-Stimulating-Factor, Macrophages: de, ph, me, Mice, Mice-Inbred-C3H, RNA: ge, SUPPORT-U-S-GOVT-P-H-S, Thymus-Gland: de, cy, me, Tumor-Necrosis-Factor: ge, ph, me

JAX Source

J Leukoc Biol 1992 Jan;51(1):93-6

Grant

CA27523

Abstract

In this brief definitive report, we show that over a 6-h period and under serum-free conditions, recombinant monocyte-macrophage colony-stimulating factor 1 (rCSF-1) and lipopolysaccharide (LPS) synergize and induce macrophages to express higher levels of mRNA for interleukin 1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor alpha (TNF-alpha), and IL-6 and to release more bioactivity than macrophages treated with LPS alone. This synergy was regulated by the amount of LPS in the culture medium. Paraformaldehyde-fixed macrophages like-wise showed augmentation of IL-1 activity, but whereas all of the bioactivity associated with the fixed macrophages could be neutralized by anti-IL-1 alpha antibody only approximately 40% of the supernate activity could be attributed to IL-1 alpha. Preliminary data suggest that the augmenting effect induced by CSF-1 cannot be explained solely on a quantitative basis because the addition of rIL-1 alpha to supernates of macrophages treated with LPS alone or with the combination of LPS and CSF-1 resulted in an increase in thymocyte mitogenic activity to a level that could not be explained on an additive basis. Although the supernates contained TNF and IL-6, antibody neutralization assays made it unlikely that these were directly responsible for the augmenting effect. These results suggest that CSF-1 not only enhances basic genetic responses induced by LPS alone but also may induce a mechanism that amplifies cytokine bioactivity.

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