An inducible nitric-oxide synthase (NOS)-associated protein inhibits NOS dimerization and activity

A variety of transcriptional and post-transcriptional mechanisms regulate t he expression of the inducible nitric-oxide synthase (iNOS, or NOS2). Altho ugh neurons and endothelial cells express proteins that interact with and i nhibit neuronal NOS and endothelial NOS, macrophage proteins that inhibit N OS2 have not been identified. We show that murine macrophages express a 110 -kDa protein that interacts with NOS2, which we call NOS-associated protein -110 kDa (NAP110). NAP110 directly interacts with the amino terminus of NOS 2, and inhibits NOS catalytic activity by preventing formation of NOS2 homo dimers. Expression of NAP110 may be a mechanism by which macrophages expres sing NOS2 protect themselves from cytotoxic levels of nitric oxide.