Nitric oxide (.NO)-induced mitochondrial injury among chicken .NO-generating and target leukocytes.
In an analysis of nitric oxide (.NO) production and toxicity, chicken macrophage-generated .NO inhibited mitochondrial activity in both .NO-producing macrophages themselves and lymphoid tumor targets. However, differences in targeting of mitochondrial toxicity were observed among these cells. Two chicken macrophage cell lines, HD11 and MQ-NCSU, produced .NO (measured as nitrite) dependent upon concentrations of L-arginine and bacterial endotoxin (lipopolysaccharide). Mitochondrial activity was negatively correlated with the amount of .NO produced. Using a modified MTT assay, .NO induced suppression in two mitochondrial complexes. Mitochondrial activity was significantly suppressed among HD11 cells receiving LPS alone (complex I, 63.0 +/- 5.5% suppression; complex II, 27.9 +/- 5.2%). In contrast, mitochondrial activities in samples receiving LPS plus inhibitor, NG-nitro-L-arginine methyl ester (NAME; 5 mM) or 2,4-diamino-6-hydroxypyrimidine (DAHP; 5 mM), were not significantly different from control values. When HD11 macrophages were cocultured with lymphoblastoid tumor targets, RECC-CU60 (T cell) or LSCC-RP9 (B cell), adding LPS (1 microgram/ml), tumor cell mitochondrial activity was significantly suppressed. In the generator macrophages, complex I was more suppressed than complex II, whereas in lymphoid targets no such difference was observed. These results indicate that .NO inhibits complex I and II mitochondrial activity but that differential targeting can occur among chicken leukocyte populations.
Institute for Comparative and Environmental Toxicology, Cornell University, Ithaca, New York 14853-5601.
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Sung
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Dietert
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D002645:Chickens; D007042:Hypoxanthines / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000494:pharmacology; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology*; D010088:Oxidoreductases / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured
D007042:Hypoxanthines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D001120:Arginine; D010088:Oxidoreductases; C017202:2,4-diaminohypoxanthine; D019331:NG-Nitroarginine Methyl Ester