Regulation and control of nitric oxide (NO) in macrophages: Protecting the “professional killer cell” from its own cytotoxic arsenal via MRP1 and GSTP1

Abstract We recently demonstrated that a novel storage and transport mechanism for nitric oxide (NO) mediated by glutathione- S -transferase P1 (GSTP1) and multidrug resistance protein 1 (MRP1/ABCC1), protects M1-macrophage (M1-MO) models from large quantities of endogenous NO. This system stores and transports NO as dinitrosyl-dithiol-iron complexes (DNICs) composed of iron, NO and glutathione (GSH). Hence, this gas with contrasting anti- and pro-tumor effects, which has been assumed to be freely diffusible, is a tightly-regulated species in M1-MOs. These control systems prevent NO cytotoxicity and may be responsible for delivering cytotoxic NO as DNICs via MRP1 from M1-MOs, to tumor cell targets.