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Low density lipoprotein oxidation by stimulated neutrophils and ferritin
D S Abdalla1, A Campa, H P Monteiro
1Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Brazil.
Abstract:
Low density lipoprotein (LDL) oxidation mediated by phorbol myristate acetate (PMA)- and formylmethionylleucylphenylalanine (FMLP) -stimulated human neutrophils was enhanced by 70% in the presence of ferritin. Iron released from ferritin by the superoxide anion generated in the respiratory burst of stimulated neutrophils is shown to be involved in lipoprotein oxidation. Ascorbate (100 microM), superoxide dismutase (10 micrograms/ml) and uric acid (430 microM) showed inhibitory effects of 30% [corrected], 70% and 50% on LDL oxidation, respectively. Ceruloplasmin (2.7 microM) potentiated LDL oxidation by stimulated neutrophils and ferritin, both alone and in the presence of methionine. Methionine (1 mM) and catalase (30 micrograms/ml) increased LDL oxidation by stimulated neutrophils and ferritin. These data suggest that LDL oxidation by stimulated neutrophils and ferritin may be relevant in inflammation when both neutrophils and ferritin are increased.
Insights
Ferritin enhances low-density lipoprotein (LDL) oxidation by neutrophils, involving iron release. Antioxidants like ascorbate inhibit this process, suggesting a role in inflammation.
Area of Science:
- Biochemistry
- Immunology
- Oxidative Stress
Background:
- Low-density lipoprotein (LDL) oxidation is implicated in various pathological conditions.
- Neutrophils play a role in inflammatory responses and can generate reactive oxygen species.
- Ferritin, an iron-storage protein, can potentially contribute to oxidative processes.
Purpose of the Study:
- To investigate the role of ferritin in neutrophil-mediated LDL oxidation.
- To elucidate the mechanisms involved in ferritin-enhanced LDL oxidation.
- To assess the impact of antioxidants and other molecules on this process.
Main Methods:
- Human neutrophils were stimulated using phorbol myristate acetate (PMA) and formylmethionylleucylphenylalanine (FMLP).
- LDL oxidation was measured in the presence and absence of ferritin and other agents.
- The effects of antioxidants (ascorbate, superoxide dismutase, uric acid) and other compounds (ceruloplasmin, methionine, catalase) were evaluated.
Main Results:
- Ferritin significantly enhanced neutrophil-mediated LDL oxidation by 70%.
- Iron released from ferritin by superoxide anions was identified as a key factor in LDL oxidation.
- Ascorbate, superoxide dismutase, and uric acid demonstrated inhibitory effects on LDL oxidation.
Conclusions:
- Neutrophil-mediated LDL oxidation is potentiated by ferritin, likely through iron release.
- Antioxidants can mitigate ferritin-induced LDL oxidation.
- These findings suggest a potential role for neutrophil- and ferritin-mediated LDL oxidation in inflammatory conditions.
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