Neutrophil leukocytes provide first-line phagocytic defense against infection. Phagocyte locomotion to the site of infection, identification, and phagocytosis of the infecting microbe results in metabolically driven O2-dependent combustive microbicidal action. NADPH oxidase activity controls this respiratory burst metabolism. Its flavoenzyme character allows semiquinone-mediated crossover from two reducing equivalents (2RE) to 1RE transfer, as is necessary for univalent reduction of O2 to the acid hydroperoxyl radical (HO2) and its conjugate base, superoxide anion (O2−). RE transfer dynamics is considered from the perspectives of quantum and particle physics, as well as frontier orbital interactions. Direct disproportionation of HO2-O2− yields electronically excited singlet molecular oxygen (1O2*) and hydrogen peroxide (H2O2). Myeloperoxidase catalyzes H2O2-dependent 2RE oxidation of chloride (Cl−) to hypochlorite (OCl−). Direct nonenzymatic reaction of OCl− with an additional H2O2 yields Cl−, H2O, and 1O2*. Thus, for two 2RE metabolized through NADPH oxidase, a total of three 1O2* are possible. H2O2, OCl−, and 1O2* generated are all singlet multiplicity reactants and can participate in spin-allowed combustive oxygenations yielding light emission, that is, luminescence or chemiluminescence. The sensitivity of luminescence for measuring neutrophil redox activities is increased several orders of magnitude by introducing chemiluminigenic probes. Probes can be selected to differentiate oxidase from haloperoxidase activities.
Part of the book: Neutrophils