Interference of target cell catalase with an early step of the neutrophil cytolytic pathway

F. Dallegri, A. Ballestrero, G. Frumento, F. Patrone

Research output: Contribution to journalArticlepeer-review

Abstract

The hypochlorous acid (HOCl)-dependent lysis of human red blood cells (HRBC) targets by neutrophils, activated with opsonized zymosan particles (OPZ), was increased by inhibiting HRBC catalatic activity with aminotriazole (AT; HRBC(AT)). The inhibition of HRBC glutathione cycle activity with carmustine (BCNU; HRBC(BCNU)) had no effect. In addition, the recovery of hydrogen peroxide (H2O2) and HOCl from neutrophils, activated under conditions similar to those used for cytotoxicity assay, was reduced by the presence of HRBC and restored by replacing HRBC with HRBC(AT), but not with HRBC(BCNU). Linear relationships were found between the increments in the neutrophil-mediated lysis, observed by using HRBC(AT) instead of HRBC, and the increments in the H2O2 or HOCl recovery, detected by replacing HRBC with HRBC(AT). Together these data, coupled with the results obtained by probing neutrophil cytolysis with chemical agents, suggest that the increased cytolytic efficiency displayed by neutrophils against HRBC(AT), inhibited in their catalatic activity, is due to an enhanced availability of neutrophil-derived H2O2, with a consequent enhancement in the HOCl production (according to the following reaction: H2O2 + Cl- (MPO)/(H+) → HOCl + H2O). Thus it appears that HRBC catalase restrains the neutrophil cytolytic activity, by interfering with an early step of the pathway through which neutrophils generate cytotoxins.

Original languageEnglish
Pages (from-to)664-670
Number of pages7
JournalClinical and Experimental Immunology
Volume65
Issue number3
Publication statusPublished - 1986

ASJC Scopus subject areas

  • Immunology

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