Induction of nitric oxide production in mouse macrophages by Shiga toxin.

Host mediators play an important role in the pathogenesis of shigellosis and Shiga toxin toxicity. Nitric oxide (NO) production in mouse peritoneal macrophages and in the macrophage J744 cell line in response to purified Shiga toxin and lipopolysaccharide (LPS) from Shigella flexneri were studied. Shiga toxin induced NO production in a dose-dependent manner up to 800 ng/ml. Detectable levels of NO were present as early as 4 h after induction and continued to increase during 72 h; Shiga toxin induced greater NO production with time than did LPS. Pre-treatment of Shiga toxin (400 ng/ml) or LPS (10 ng/ml) with polymyxin B, which inactivates LPS, reduced their ability to induce NO by 28% and 96%, respectively. Induction in the presence of anti-TNF alpha antibodies did not reduce the amount of NO in the supernate. These studies showed that Shiga toxin induces NO production in murine macrophages.