Reactive species at the phagosome. (A) In macrophages (phagosome pH ≤ 5), NADPH oxidase activation (blue sphere) leads to O₂^•− generation toward the phagocytic vacuole (1). O₂^•− dismutates to H₂O₂ (2) and/or protonates to generate HO^•₂ radical (3). O₂^•− may reach the pathogen by means of anion channels, whereas both H₂O₂ and HO₂^• can diffuse across membranes. Immune-stimulated macrophages expressing iNOS (red sphere) produce ^•NO (4), which diffuses to the phagosome while reacting fast with O₂^•− (5) to yield peroxynitrite anion (ONOO⁻). ONOO⁻ can protonate to peroxynitrous acid (ONOOH); it also permeates the parasite and reacts with CO₂ (6) to yield ^•NO₂ and CO₃^•− radicals (inset). Both ONOO⁻ and ONOOH (7) promote the oxidation and nitration of membrane lipids and proteins (8). (B) In neutrophils (phagosome pH ≥ 7.5), MPO-derived HOCl is the dominant oxidant generated in this phagocyte (3) and promotes oxidation and chlorination reactions (9). Although the de novo production of ^•NO (4) by human neutrophils has rarely been documented, ^•NO may arise from exogenous sources existing in inflammatory foci and permeate the neutrophil plasma membrane. The other numbers in B denote the same processes described above for A.