Nitric oxide (#{149}NO)-inducedmitochondrial injury among chicken #{149}NO-generatingand target leukocytes

In an analysis of nitric oxide ( . NO) production and toxicity, chicken macrophage-generated #{149} 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 #{149} NO (measured as nitrite) dependent upon concentrations of L-arginine and bacterial endotoxin (lipopolysaccharide). Mitochondrial activity was negatively correlated with the amount of #{149} NO produced. Using a modified MTT assay, #{149} NO induced suppression in two mitochondrial cornplexes. Mitochondrial activity was significantly suppressed among HD11 cells receiving LPS alone (complex I, 63.0 ± 5.5% suppression; complex II, 27.9 ± 52%). 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-CU6O (T cell) or LSCC-RP9 (B cell), adding LPS (1 tg/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 #{149} NO inhibits complex I and II mitochondnial activity but that differential targeting can occur among chicken leukocyte populations. J. Leukoc. Biol. 56: 52-58; 1994.