Infection and Nitric Oxide

The author describes how his experience as an infectious disease fellow at Stanford University with Jack Remington from 1969 to 1971 influenced the direction of his subsequent laboratory investigation. The author reviews a series of studies that were intended to provide a mechanistic understanding of an in vitro cytotoxicity assay developed while he was a fellow with Jack Remington. These investigations resulted in the 1987 discovery of the synthesis of nitric oxide from L-arginine by cytokine-activated macrophages. This work provided the components (the precursor, products, and an inhibitor) of the enzymatic synthesis of nitric oxide by all three later-identified nitric oxide synthase isoforms. The significance of cytokine-induced nitric oxide synthesis during innate resistance and cell-mediated immune reactions is discussed briefly.