the heart is an early target of anthrax lethal toxin in mice a protective role for neuronal nitric oxide synthase (nnos)心脏是炭疽致命毒素的早期目标神经元一氧化氮合酶在小鼠的保护作用(nnos).pdf

The Heart Is an Early Target of Anthrax Lethal Toxin in Mice: A Protective Role for Neuronal Nitric Oxide Synthase (nNOS) 1 1 2 2 3 4 Mahtab Moayeri , Devorah Crown , David W. Dorward , Don Gardner , Jerrold M. Ward , Yan Li , 4 4 1 Xizhong Cui , Peter Eichacker , Stephen H. Leppla * 1 Bacterial Toxins and Therapeutics Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 2 Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America, 3 Infectious Diseases Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America, 4 Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, Maryland, United States of America Abstract Anthrax lethal toxin (LT) induces vascular insufficiency in experimental animals through unknown mechanisms. In this study, we show that neuronal nitric oxide synthase (nNOS) deficiency in mice causes strikingly increased sensitivity to LT, while deficiencies in the two other NOS enzymes (iNOS and eNOS) have no effect on LT-mediated mortality. The increased sensitivity of nNOS2/ 2 mice was independent of macrophage sensitivity to toxin, or cytokine responses, and could be replicated in nNOS-sufficient wild-type (WT) mice through pharmacological inhibition of the enzyme with 7-nitroindazole. Histopathological analyses showed that LT induced architectura