Effect of overexpression of human Cu,Zn superoxide dismutase in transgenic mice on macrophage functions.
Properties of macrophages from transgenic mice with the human Cu,Zn superoxide dismutase (SOD) gene under the control of the mouse hydroxyl-methyl coenzyme A reductase (HMGCR) promoter were studied. In these mice, a twofold overproduction of Cu,Zn SOD in intraperitoneal macrophages resulted in the significant reduction of their microbicidal and fungicidal activity. Intracellular production and release of H2O2 in macrophages from transgenic mice activated by PMA was found to be significantly increased, whereas extracellular release of O2- was inhibited. When treated with LPS or LPS plus IFN-gamma, macrophages from transgenic mice were found to produce less nitric oxide (NO) than normal mice, suggesting that the nitrocompound metabolism in macrophages overproducing Cu,Zn SOD was also affected. Analysis of NF-kappa B DNA-binding activity and antiphosphotyrosine immunoblotting experiments suggest that impairment of macrophage functions may be attributed to the inhibition of signal transduction pathways as well as to changes in oxygen radical metabolism. The present data support the notion that antioxidant enzymes play important roles in the function of macrophages.
Mirochnitchenko
O
O
Department of Biochemistry, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854, USA.
Inouye
M
M
D000818:Animals; D001483:Base Sequence; D001770:Blood Bactericidal Activity; D002467:Cell Nucleus / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004314:Down Syndrome / Q000503:physiopathology; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010587:Phagocytosis; D019000:Phosphotyrosine / Q000378:metabolism; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000502:physiology*
D017931:DNA Primers; D016328:NF-kappa B; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D019000:Phosphotyrosine; D013482:Superoxide Dismutase