Neutrophil-induced depletion of adenosine triphosphate in target cells; Evidence for a hypochlorous acid-mediated process

Franco Dallegri, Riccardo Goretti, Alberto Ballestrero, Luciano Ottonello, Franco Patrone

Research output: Contribution to journalArticle

Abstract

Human neutrophils, Incubated with phorbol myristate acetate (PMA), cause a rapid and substantial adenosine triphosphate (ATP) depletion In lymphoblostold Daudi cells without producing lysls. Catalase (which destroys hydrogen peroxide), taurine and methlonine (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 neutrophlls with an appropriate myeloperoxidase-H202-Cl- enzymatic system. Together, these data suggest that the neutrophil ATP depleting activity involves the myeloperoxidase-catalyzed transformation of HO, Into HOCI. Moreover, the free H2O2 remaining In the neutrophil extracellular environment is ineffective. In fact, a comparable amount of enzymatically generated 1160, did not cause Daudi cell ATP loss. A direct role for H2O2 in the neutrophil-Induced Daudl cell ATP depletion was observed only under artificial conditions, that is, in the presence of the hems enzyme inhibitor azide, which prevented the HOCI production but dramatically augmented the extracellular H202 level. Similar levels of ATP-depletion in Daudi cells were induced by amounts of reagent HOCI comparable to those generated by neutrophils. As the generated HOCI can rapidly react with a variety of neutrophll-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 monochioramhte, 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 HOCI-dependent, is not mediated by NH2CI or TauNHCI, and could be promoted either by HOCI directly or by an unknown derivative oxidant. Finally, ammonia and taurine, two amines released by neutrophils, act as down-regulators of the process by trapping a fraction of the general HOCI to yield chloramines that were Ineffective in depleting ATP under the conditions studied.

Original languageEnglish
Pages (from-to)765-772
Number of pages8
JournalThe Journal of Laboratory and Clinical Medicine
Volume112
Issue number6
Publication statusPublished - 1988

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ASJC Scopus subject areas

  • Medicine(all)
  • Pathology and Forensic Medicine

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