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Myeloperoxidase secretion during phagocytosis: a case of a patient with impaired bactericidal activity
S W Edwards1, J E Say, J Taylor
1Department of Biochemistry, University of Liverpool, UK.
Abstract:
We describe a case of a 5-year-old male patient with prolonged and extensive osteomyelitis of the left femur. Staphylococcus aureus was grown from blood cultures taken upon admission and also from pus drained from an incised hip joint. A defect in immune function was suspected and neutrophil function was assessed. Chemotaxis and phagocytosis were normal, but phagocytosed S. aureus were not killed as efficiently as in control neutrophils. No inherent defect in the ability of these neutrophils to generate reactive oxidants was observed, but an unusual luminol-dependent chemiluminescence response was obtained during phagocytosis of latex beads or opsonized S. aureus: This was characterized by an initial rapid, but transient increase occurring within 1 min of addition of phagocytic stimulus. Whereas during phagocytosis of latex beads by control neutrophils less than 1% of the total myeloperoxidase activity was detected extracellularly, up to 15% was released from the patient's neutrophils. We propose that release of myeloperoxidase from the patient's neutrophils during phagocytosis reduces the intraphagosomal concentration of this enzyme and thus impairs the efficiency of intracellular killing of S. aureus.
Insights
This study details a pediatric case of severe femur osteomyelitis caused by Staphylococcus aureus. Neutrophils showed impaired killing of bacteria due to excessive myeloperoxidase release during phagocytosis.
Area of Science:
- Immunology
- Pediatric Infectious Diseases
- Molecular Biology
Background:
- Osteomyelitis is a severe bone infection, often caused by Staphylococcus aureus.
- Neutrophil dysfunction can lead to recurrent or persistent infections.
- Assessing neutrophil function is crucial for diagnosing immunodeficiencies.
Observation:
- A 5-year-old male presented with extensive left femur osteomyelitis and Staphylococcus aureus infection.
- Neutrophil phagocytosis was normal, but bacterial killing was impaired.
- An abnormal, transient luminol-dependent chemiluminescence response was observed during phagocytosis.
Findings:
- Patient neutrophils exhibited normal reactive oxidant generation but released significantly higher levels of myeloperoxidase (MPO) extracellularly during phagocytosis.
- Up to 15% of total MPO activity was released extracellularly by patient neutrophils, compared to <1% in controls.
- This excessive MPO release likely reduces intracellular MPO concentration, impairing bacterial killing.
Implications:
- This case highlights a novel mechanism of neutrophil dysfunction potentially leading to severe, persistent bacterial infections.
- Understanding MPO release defects may offer new diagnostic or therapeutic targets for recurrent infections.
- Further research into extracellular MPO release in pediatric osteomyelitis is warranted.