Role of reactive O2 in phagocyte-induced hypermetabolism and pulmonary injury

A. A. Vlessis, D. Bartos, P. Muller, D. D. Trunkey

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Activated phagocytes possess an enormous capacity for O2 consumption via NADPH oxidase. NADPH oxidase partially reduces O2, forming superoxide (O2/-). Host enzymes rapidly complete O2/- reduction to H2O, leaving little trace of its prior existence. Our objectives were to estimate the magnitude of whole body phagocyte respiration and determine the contribution of NADPH-derived O2 to the ensuing phagocyte-induced pulmonary injury. These objectives were accomplished using specific inhibitors of NADPH oxidase, diphenyl iodonium (DPI) and di-2-thienyl iodonium (DTI). Guinea pigs received intravenous injections of DPI (3.5 mg/kg), DTI (7.5 mg/kg), or vehicle followed by phorbol myristate acetate (PMA). Phagocyte activation by PMA immediately increased whole body respiration from 13.6 to 16.1 ml O2 · kg- 1 · min-1 (P < 0.05). DPI and DTI completely blocked the increase in respiration induced by PMA injection (P < 0.05). Baseline respiration was unchanged by the NADPH oxidase inhibitor alone. Likewise, there was no effect on the respiration of isolated heart and kidney mitochondria from animals receiving the inhibitor with or without PMA. DPI attenuated the pulmonary injury induced by PMA. The ratio of lung water weight to dry weight was lower (6.4 ± 0.3 vs. 8.3 ± 0.6) and arterial PO2 was higher (86 ± 9 vs. 56 ± 6 Torr) in animals receiving DPI plus PMA than in those receiving PMA alone. In conclusion, phagocyte activation in vivo increased total body respiration by ~18%. The burst in respiration is attributed to the phagocyte respiratory burst in which NADPH oxidase partially reduces O2 to O2. This corresponds to a O2 generation rate of ~210 μmol · kg-1 · min-1, which is a significant load for host detoxification systems. In addition, NADPH-oxidase derived O2/- contributes to the pulmonary injury induced by phagocyte activation.

Original languageEnglish (US)
Pages (from-to)112-116
Number of pages5
JournalJournal of Applied Physiology
Volume78
Issue number1
DOIs
StatePublished - 1995

Keywords

  • iodonium
  • peroxide
  • respiration
  • sepsis
  • superoxide

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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