FIG. 4.

Diffusion of nitric oxide into the phagolysosome and the recycling of peroxynitrite-derived nitrite. Only a miniscule volume of extracellular fluid is engulfed into phagocytic vacuoles, which provides a limited amount of chloride as a substrate for myeloperoxidase. In contrast, nitric oxide can readily diffuse into the phagolysosome. Neutrophils produce superoxide by NADPH oxidases, but superoxide is unlikely to penetrate cell membranes or cell walls of pathogens, and can reversibly inactivate myeloperoxidase. Peroxynitrite is a substrate for myeloperoxidase and can reverse this inhibition. In addition, nitrite formed from peroxynitrite decomposition is entrapped within the phagolysosome and serves as an additional substrate for myeloperoxidase. Myeloperoxidase is not a predominant protein in macrophages, where formation of peroxynitrite from superoxide and nitric oxide appears to be a major mechanism of cytotoxicity.