- Description
- Phagocytes (e.g., neutrophils, monocytes) ingest pathogens
- Activation of the NADPH oxidase complex generates and releases reactive oxygen species (ROS; free radicals) that destroy the pathogens in phagosomes
- Mechanism
- 1. NADPH Oxidase (located on the phagosome membrane)
- This is the rate-limiting enzyme and the first step.
- Converts molecular oxygen (O₂) to superoxide (O₂•⁻).
- Reaction:
O₂ + NADPH → O₂•⁻ + NADP⁺ + H⁺
- A large amount of NADPH is consumed, leading to ↑ activity in the pentose phosphate pathway (HMP shunt) to regenerate NADPH.
- 2. Superoxide Dismutase (SOD)
- Converts superoxide to hydrogen peroxide (H₂O₂).
- Reaction:
2O₂•⁻ + 2H⁺ → H₂O₂ + O₂
- 3. Myeloperoxidase (MPO)
- An enzyme contained within azurophilic granules of neutrophils.
- Converts H₂O₂ to hypochlorous acid (HOCl, i.e., bleach), a potent antimicrobial agent. MPO gives sputum its characteristic green color.
- Reaction:
H₂O₂ + Cl⁻ + H⁺ → HOCl + H₂O
- Release of oxidative burst causes K+ influx, which triggers secretion of lysosomal enzymes into the phagosome.
| Rank | ROS Species | Potency/Reactivity | Key USMLE Fact |
|---|
| 1 | Hydroxyl Radical (•OH) | Extreme | Most biologically reactive ROS; formed from H2O2 via the Fenton Reaction (non-enzymatic process). |
| 2 | Hypochlorous Acid (HOCl) | Very High | ”Bleach”; produced by myeloperoxidase in neutrophils to kill pathogens. |
| 3 | Superoxide (O2•⁻) | Moderate | Initial ROS made by NADPH oxidase in the respiratory burst. |
| 4 | Hydrogen Peroxide (H2O2) | Low | Stable precursor to •OH and HOCl; can diffuse across membranes. |
- Clinical significance
- Respiratory burst is a vital component of innate immune response
- Impaired respiratory burst leads to an elevated risk of infection with catalase-positive pathogens (e.g., Aspergillus, S. aureus).
- Normally, phagocytes can transform H2O2 generated by invading pathogens into ROS.
- Catalase-positive organisms can degrade their own H2O2, leaving phagocytes without substrate to convert.
- P. aeruginosa uses pyocyanin to form ROS and eliminate competing organisms.