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Inhibition of colony-stimulating factor-stimulated macrophage proliferation by tumor necrosis factor-alpha, IFN-gamma, and lipopolysaccharide is not due to a general loss of responsiveness to growth factor.
J Immunol. 1991 May 15; 146(10):3469-77.JI

Abstract

The role of stimulatory factors, such as the CSF, in the regulation of hemopoiesis has been extensively documented. Less is known of the negative regulators of hemopoiesis. In this report, we show that the macrophage activating agents, TNF-alpha, IFN-gamma, and LPS, are all potent inhibitors of CSF-1-stimulated murine bone marrow-derived macrophage (BMM) DNA synthesis and increase in cell numbers. The inhibitory effects of TNF-alpha and IFN-gamma do not appear to be due to endotoxin contamination in the recombinant cytokine preparations. The inhibition of proliferation is reversible and is not due to a general loss of growth factor responsiveness, inasmuch as the three agents do not inhibit CSF-1-stimulated BMM survival, protein synthesis, or fluid phase pinocytosis. Because TNF-alpha and LPS are known to rapidly and potently down-modulate CSF-1 receptor levels in BMM, the results also suggest that low levels of receptor occupancy are sufficient for biological responses to CSF-1. The inhibitory effects of TNF-alpha, IFN-gamma, or LPS were also seen when granulocyte-macrophage-CSF or IL-3 was used to stimulate BMM DNA synthesis. The results suggest that TNF-alpha, IFN-gamma, and LPS appear to be inhibiting CSF-stimulated proliferation by acting at a post-receptor level, possibly by regulation of some critical event(s) in the mitogenic signaling pathway.

Authors+Show Affiliations

University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Australia.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1902855

Citation

Vairo, G, et al. "Inhibition of Colony-stimulating Factor-stimulated Macrophage Proliferation By Tumor Necrosis Factor-alpha, IFN-gamma, and Lipopolysaccharide Is Not Due to a General Loss of Responsiveness to Growth Factor." Journal of Immunology (Baltimore, Md. : 1950), vol. 146, no. 10, 1991, pp. 3469-77.
Vairo G, Argyriou S, Knight KR, et al. Inhibition of colony-stimulating factor-stimulated macrophage proliferation by tumor necrosis factor-alpha, IFN-gamma, and lipopolysaccharide is not due to a general loss of responsiveness to growth factor. J Immunol. 1991;146(10):3469-77.
Vairo, G., Argyriou, S., Knight, K. R., & Hamilton, J. A. (1991). Inhibition of colony-stimulating factor-stimulated macrophage proliferation by tumor necrosis factor-alpha, IFN-gamma, and lipopolysaccharide is not due to a general loss of responsiveness to growth factor. Journal of Immunology (Baltimore, Md. : 1950), 146(10), 3469-77.
Vairo G, et al. Inhibition of Colony-stimulating Factor-stimulated Macrophage Proliferation By Tumor Necrosis Factor-alpha, IFN-gamma, and Lipopolysaccharide Is Not Due to a General Loss of Responsiveness to Growth Factor. J Immunol. 1991 May 15;146(10):3469-77. PubMed PMID: 1902855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of colony-stimulating factor-stimulated macrophage proliferation by tumor necrosis factor-alpha, IFN-gamma, and lipopolysaccharide is not due to a general loss of responsiveness to growth factor. AU - Vairo,G, AU - Argyriou,S, AU - Knight,K R, AU - Hamilton,J A, PY - 1991/5/15/pubmed PY - 1991/5/15/medline PY - 1991/5/15/entrez SP - 3469 EP - 77 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 146 IS - 10 N2 - The role of stimulatory factors, such as the CSF, in the regulation of hemopoiesis has been extensively documented. Less is known of the negative regulators of hemopoiesis. In this report, we show that the macrophage activating agents, TNF-alpha, IFN-gamma, and LPS, are all potent inhibitors of CSF-1-stimulated murine bone marrow-derived macrophage (BMM) DNA synthesis and increase in cell numbers. The inhibitory effects of TNF-alpha and IFN-gamma do not appear to be due to endotoxin contamination in the recombinant cytokine preparations. The inhibition of proliferation is reversible and is not due to a general loss of growth factor responsiveness, inasmuch as the three agents do not inhibit CSF-1-stimulated BMM survival, protein synthesis, or fluid phase pinocytosis. Because TNF-alpha and LPS are known to rapidly and potently down-modulate CSF-1 receptor levels in BMM, the results also suggest that low levels of receptor occupancy are sufficient for biological responses to CSF-1. The inhibitory effects of TNF-alpha, IFN-gamma, or LPS were also seen when granulocyte-macrophage-CSF or IL-3 was used to stimulate BMM DNA synthesis. The results suggest that TNF-alpha, IFN-gamma, and LPS appear to be inhibiting CSF-stimulated proliferation by acting at a post-receptor level, possibly by regulation of some critical event(s) in the mitogenic signaling pathway. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/1902855/Inhibition_of_colony_stimulating_factor_stimulated_macrophage_proliferation_by_tumor_necrosis_factor_alpha_IFN_gamma_and_lipopolysaccharide_is_not_due_to_a_general_loss_of_responsiveness_to_growth_factor_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=1902855 DB - PRIME DP - Unbound Medicine ER -