The Multiplex Function of Nitric Oxide in (Auto)immunity

Study of the role of nitric oxide (NO) in mammalian organisms has a history of complexities. When eukaryotic cells were demonstrated to generate NO from the aminoacid l-arginine, we were first stunned and then fascinated by the idea that a molecule with such a simple structure exerts messenger functions and regulates complex life processes. Soon, however, we had to learn that there are at least three different isoforms of nitric oxide synthases (NOS), which all catalyze the same redox reaction, but differ in biochemical and structural properties, output of NO, function, distribution, and regulation (1, 2). The introduction of the acronyms ncNOS, iNOS, and ecNOS helped us to memorize that the type 1 NOS is constitutively expressed in neurons, where its activity is regulated by Ca²⁺ gradients and is critical for neurotransmission and learning; that the type 2 NOS is transcriptionally induced by cytokines,...