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Neutrophils from patients with secondary haemosiderosis contain excessive amounts of autotoxic iron
B Cantinieaux1, J R Boelaert, J De Meuleneire
1Department of Hematology, Hôpital Saint-Pierre, Université Libre de Bruxelles, Belgium.
Abstract:
Secondary haemosiderosis may be accompanied by a decrease in the phagocytic function of neutrophils (PMNs). This dysfunction has been attributed to an exaggerated generation of oxidants induced by intracellular iron. However, an accumulation of iron has so far not been reliably demonstrated in neutrophils harvested from iron-overloaded patients. Six polytransfused haemodialysed patients, with a serum ferritin level higher than 1000 micrograms/l, and 10 healthy controls were investigated. The iron status of PMNs was evaluated by iron determination using atomic absorption spectrometry and by ferritin measurement using radioimmunoassay. The phagocytic performance was measured by cytofluorometry. The results confirm that PMNs from the haemosiderosis patients have a decreased phagocytosis. Moreover, they demonstrate for the first time that these PMNs have an increased cellular iron and ferritin content. Both latter concentrations were 4 to 5 times more elevated in secondary haemosiderosis than in healthy controls. This iron accumulation may be toxic for the PMNs and may, at least partially, explain the three-fold higher risk of bacteraemia which has been reported in those patients.
Insights
Patients with secondary haemosiderosis show reduced neutrophil (PMN) phagocytosis due to increased intracellular iron. This study confirms iron accumulation in neutrophils, explaining impaired immune function and higher infection risk in these patients.
Area of Science:
- Hematology
- Immunology
- Clinical Biochemistry
Background:
- Secondary haemosiderosis is linked to decreased neutrophil phagocytic function.
- This dysfunction is hypothesized to stem from excessive oxidants induced by intracellular iron.
- Previous studies have not reliably demonstrated iron accumulation in neutrophils of iron-overloaded patients.
Purpose of the Study:
- To investigate iron status and phagocytic function in neutrophils of patients with secondary haemosiderosis.
- To determine if intracellular iron accumulation occurs in neutrophils of these patients.
- To explore the relationship between iron accumulation, neutrophil dysfunction, and infection risk.
Main Methods:
- Studied six polytransfused hemodialysis patients with high serum ferritin and ten healthy controls.
- Assessed neutrophil (PMN) iron and ferritin content using atomic absorption spectrometry and radioimmunoassay.
- Measured phagocytic performance via cytofluorometry.
Main Results:
- Neutrophils from haemosiderosis patients exhibited decreased phagocytosis.
- Demonstrated significantly increased cellular iron and ferritin content in neutrophils of these patients (4-5 times higher than controls).
- Confirmed iron accumulation in neutrophils of patients with secondary haemosiderosis.
Conclusions:
- Neutrophil iron overload in secondary haemosiderosis impairs phagocytic function.
- This iron accumulation may contribute to the elevated risk of bacteremia observed in these patients.
- Provides the first direct evidence of iron accumulation within neutrophils in secondary haemosiderosis.