Effects of hydrogen peroxide on neutrophil ability to generate reactive oxygen and chlorine species and to secrete myeloperoxidase in vitro

In this work, the effects of H₂O₂ at concentrations of 10^?8–10^?2 mol/l on the neutrophil ability to generate reactive oxygen and chlorine species (ROCS) and to secrete myeloperoxidase (MPO) were studied, as well as the H₂O₂ damaging action on neutrophils. It was found that H₂O₂ at concentrations of 2 × 10^?3–10^?2 mol/l led to disturbances of neutrophil membrane barrier properties and to a lactate dehydrogenase release. Incubation of neutrophils with an addition of 10^?4–10^?7 mol/l H₂O₂ was accompanied by an increase of the cell ability to generate ROCS during phagocytosis and a decrease of neutrophil ability to secrete MPO and ROCS into the extracellular medium during adhesion. Mechanisms of the H₂O₂ action are coupled with arachidonic acid metabolism. Inhibition of the 5-lipoxygenase or cyclooxygenase metabolism pathways produced an enhancement of the H₂O₂ destructive effect. Block of 5-lipoxygenase pathway led to elimination of the H₂O₂ action on MPO and ROCS secretion and to an enhancement of the H₂O₂ effect on the neutrophil ability to generate ROCS during phagocytosis. The obtained data indicate a high blood neutrophil resistance to the H₂O₂ destructive action and confirm the H₂O₂ regulatory role with respect to the neutrophil functions.