’Of mice and men’: Arginine metabolism in human macrophages

Macrophages are involved in inflammation from induction to resolution. Polarization of macrophages along the M1 (classical) or M2(alternative) axis occurs during inflammation and can be at least partly categorized by the route of arginine metabolism within the macrophage, balancing the activities of the arginase and nitric oxide synthase (NOS) enzyme families. Arginase activity is associated with tissue repair responses (via ornithine production and pro-proliferative effects). In contrast, NOS2 generates nitric oxide (NO) species with anti-proliferative effects that is necessary for protection against pathogens and aberrant cells. Other NOS enzymes produce NO that acts in the regulation of smooth muscle tone and other cellular processes. Macrophages preferentially expressing the arginase or NOS2 pathways enzymes also influence T-cell activation, proliferation, signaling, and apoptosis in different ways.