Alveolar macrophage cytotoxicity for normal lung fibroblasts is mediated by nitric oxide release
| Autor: | Daniel L. Morgan, Cassandra J. Shines |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide Cell Survival Cell Culture Techniques Drug Evaluation Preclinical Nitric Oxide Toxicology Nitric oxide Rats Sprague-Dawley Superoxide dismutase Interferon-gamma chemistry.chemical_compound Peroxynitrous Acid Macrophages Alveolar Animals Viability assay Lung Dose-Response Relationship Drug biology Superoxide Dismutase Tumor Necrosis Factor-alpha Superoxide Drug Synergism General Medicine Fibroblasts Molecular biology Coculture Techniques Culture Media Rats Drug Combinations NG-Nitroarginine Methyl Ester chemistry Biochemistry Alveolar macrophage biology.protein Tyrosine Tumor necrosis factor alpha Nitric Oxide Synthase Peroxynitrite Interleukin-1 |
| Zdroj: | Toxicology in Vitro. 18:139-146 |
| ISSN: | 0887-2333 |
| DOI: | 10.1016/j.tiv.2003.08.007 |
| Popis: | Nitric oxide (NO) released by activated alveolar macrophages (AM) can mediate effects on target cells and can also react with superoxide anion (O2-) to form peroxynitrite (PN), a highly cytotoxic product. The role of NO and PN in AM cytotoxicity for normal lung cells was investigated using co-cultures of rat lung fibroblasts (FB) and rat AM treated with lipopolysaccharide + interferon-gamma (LI). AM and FB, alone and in co-culture, were treated with LI for 5 days and cell viability measured. The culture media was analyzed for NO, TNF-alpha, O2-, and IL-1beta. A decreased FB viability was correlated with increased NO release by LI-activated AM. Pretreatment of co-cultures with the inducible NOS inhibitor L-NAME caused dose-related decreases in NO release by AM and increases in FB viability. Although TNF-alpha release was increased in co-cultures treated with LI, the viability of FB was not affected when cultures were treated with similar concentrations of TNF-alpha in the absence of AM. O2- could not be detected in the media and addition of superoxide dismutase (SOD) did not protect FB. These data suggest that neither O2- nor PN contributed to the loss of cell viability. Activated AM may kill normal rat lung FB through a NO-mediated pathway that does not involve PN. |
| Databáze: | OpenAIRE |
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