Hydrogen peroxide mediated killing of bacteria

Summary Polymorphonuclear leukocytes (PMN) or neutrophils have multiple systems available for killing ingested bacteria. Nearly each of these incorporates H₂O₂ indicating the essential nature of this reactive oxygen intermediate for microbicidal activity. Following ingestion of bacteria by PMN, H₂O₂ is formed by the respiratory burst which consumes O₂ and generates H₂O₂ from O_2–. H₂O₂ is deposited intracellularly near bacteria within phagocytic vacuoles where it can react with the MPO-H₂O₂-halide system to form toxic hyperchlorous acid (HOCl) and/or possibly singlet oxygen (¹O₂). H₂O₂ can also react with O_2– and/or iron (Fe⁺⁺) from lactoferrin or bacteria to form the highly toxic hydroxyl radical (¹OH). These mechanisms appear important since deficiencies of H₂O₂ production, myeloperoxidase or lactoferrin frequently increases their owner's susceptibility to infection. In particular, examination of PMN from infection prone patients with chronic granulomatous disease (CGD) most clearly demonstrates the importance of H₂O₂ in killing of bacteria. CGD PMN lack the capacity to effectively generate H₂O₂ and subsequently have impaired ability to kill catalase positive (H₂O₂ producing) but not catalase negative (not H₂O₂ producing) bacteria. PMN also have catalase and glutathione peroxidase systems in their cytoplasms to protect themselves from the toxicity of H₂O₂. Finally, while H₂O₂ is critical for host defense, it can also be released extracellularly and thereby play a significant role in PMN mediated tissue injury.