Decreased macrophage-mediated cytotoxicity in mammary-tumor-bearing mice is related to alteration of nitric-oxide production and/or release

Authors

  • Eduardo M. Sotomayor,

    1. Department of Microbiology and Immunology and the Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida, USA
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  • Michael R. Dinapoli,

    1. Department of Microbiology and Immunology and the Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida, USA
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  • Cesar Calderón,

    1. Department of Microbiology and Immunology and the Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida, USA
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  • Arthur Colsky,

    1. Department of Microbiology and Immunology and the Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida, USA
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  • Yang-Xin Fu,

    1. Department of Microbiology and Immunology and the Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida, USA
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  • Diana M. Lopez

    Corresponding author
    1. Department of Microbiology and Immunology and the Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida, USA
    • Department of Microbiology and Immunology, University of Miami School of Medicine. P.O. Box 016960 (R-138), Miami. FL 33101, USA. Fax: (305) 548-4409
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Abstract

Peritoneal-exudate macrophages (PEM) from mammarytumor-bearing mice have impaired cytotoxic activity against syngeneic and allogeneic tumor targets. The ability of PEM from normal and tumor-bearing mice to bind tumor targets was found to be similar in the presence or the absence of surrogate receptors, which enhanced the binding but not the killing of tumor targets by PEM from tumor-bearing mice, suggesting that other mechanisms are involved in their impaired cytolytic activity. Soluble and membrane-bound TNF-α, as well as H2O2, were found in higher amounts in PEM from tumor bearers upon stimulation with LPS, as compared with PEM from normal mice. However, tumor-bearers' macrophages displayed decreased capacity to produce and/or release nitric oxide, which could be reversed by the addition of increasing levels of IFN-γ. These results indicate that the lack of macrophage cytotoxicity in mammary-tumor-bearing mice is related to impaired production and/or release of NO by these effector cells, possibly aggravated by the insufficient IFN-γ production previously reported in these animals. Moreover, mammary-tumor progression results in dis-regulation of synthesis of macrophage-mediators, with over-production of molecules to which mammary-tumor cells are insensitive and deficient production of NO, the crucial molecule to which these cells appear to be highly sensitive.

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