Neutrophil-induced depletion of adenosine triphosphate in target cells: evidence for a hypochlorous acid-mediated process.

Human neutrophils, incubated with phorbol myristate acetate (PMA), caused a rapid and substantial adenosine triphosphate (ATP) depletion in lymphoblastoid Daudi cells without producing lysis. Catalase (which destroys hydrogen peroxide), taurine and methionine (which scavenge hypochlorous acid), and chloride omission from the medium prevented the ATP fall. An ATP depletion comparable to that induced by neutrophils was observed by replacing neutrophils with an appropriate myeloperoxidase-H2O2-Cl- enzymatic system. Together, these data suggest that the neutrophil ATP depleting activity involves the myeloperoxidase-catalyzed transformation of H2O2 into HOCl. Moreover, the free H2O2 remaining in the neutrophil extracellular environment is ineffective. In fact, a comparable amount of enzymatically generated H2O2 did not cause Daudi cell ATP loss. A direct role for H2O2 in the neutrophil-induced Daudi cell ATP depletion was observed only under artificial conditions, that is, in the presence of the heme enzyme inhibitor azide, which prevented the HOCl production but dramatically augmented the extracellular H2O2 level. Similar levels of ATP depletion in Daudi cells were induced by amounts of reagent HOCl comparable to those generated by neutrophils. As the generated HOCl can rapidly react with a variety of neutrophil-derived nitrogenous compounds (primarily ammonia and taurine) to yield chloramines, these chlorinated oxidants might contribute to the neutrophil-mediated ATP depletion. Nevertheless, the main and well-characterized chloramines (ammonia-derived monochloramine, NH2Cl, and taurine monochloramine, TauNHCl) were devoid of ATP-depleting capacity. Thus, the results suggest that the neutrophil-induced ATP depletion in Daudi cells is HOCl-dependent, is not mediated by NH2Cl or TauNHCl, and could be promoted either by HOCl directly or by an unknown derivative oxidant.(ABSTRACT TRUNCATED AT 250 WORDS)