Nitric oxide (NO) is an effector of the innate immune system. The innate immune system is a set of rapid host responses to pathogens. Cells of the innate immune system - macrophages, neutrophils and natural killer cells - use pattern recognition receptors to recognize molecular patterns associated with pathogens (Medzhitov, 2001). Activated macrophages then inhibit pathogen replication by releasing a variety of effector molecules, including NO.
Resting immune cells lack the inducible NO synthase (iNOS or NOS2), the enzyme that synthesizes NO. However, a variety of extracellular stimuli can activate distinct signaling pathways that converge to initiate expression of NOS2. Cell wall components of bacteria and fungi can trigger the innate immune signaling cascade, leading to expression of NOS2. For example, lipopolysaccharide (LPS), a component of the wall of Gram-negative bacteria, can bind to LPS-binding protein (LBP), which delivers LPS to CD14, a high-affinity LPS receptor. Toll-like receptor...
