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Deferoxamine enhances phagocytic function of human polymorphonuclear leukocytes
Abstract:
Inhibition of the iron-mediated generation of toxic oxygen species by polymorphonuclear leukocytes (PMN) might prevent oxidative damage and thus enhance phagocytic function of PMN. To investigate this point, we studied the effect of the specific iron chelator, deferoxamine, on the antibacterial function of PMN. PMN were incubated for 20 hr with various concentrations of deferoxamine at 37 degrees C in medium containing 0.54 microM endogenous iron. The cells were then washed, and the phagocytic cell function was assessed. The results were compared with those for control PMN preincubated for 20 hr without deferoxamine, and those of nonincubated PMN. Compared with that of control PMN, the uptake of radiolabeled Staphylococcus aureus by PMN treated with 1 microM-1 mM deferoxamine was, on average, 10%-20% higher. This effect was not observed when iron-saturated deferoxamine (DFO) was used. Bacterial uptake was similarly increased in nonpreincubated PMN or PMN preincubated for 20 hr at 4 degrees C instead of 37 degrees C. The intracellular killing capacity of both deferoxamine-treated and control PMN exceeded 90%. PMN incubated for 20 hr at 37 degrees C with DFO not only phagocytosed more bacteria than control cells, but were also capable of killing the greater number of bacteria ingested. This increased activity of deferoxamine-treated PMN was accompanied by enhanced generation of chemiluminescence and production of superoxide during phagocytosis of S. aureus. These findings indicate that deferoxamine may enhance the antibacterial activity of PMN by protecting the cells against damage by iron-mediated generation of toxic oxygen metabolites in resting PMN.
Insights
Deferoxamine, an iron chelator, enhances polymorphonuclear leukocyte (PMN) antibacterial function by preventing iron-induced oxidative damage. This improves bacterial uptake and killing capacity in PMNs.
Area of Science:
- Immunology
- Biochemistry
- Cell Biology
Background:
- Polymorphonuclear leukocytes (PMNs) generate toxic oxygen species, which can cause oxidative damage.
- Iron plays a role in the generation of these toxic oxygen species.
- Inhibiting iron-mediated damage may enhance PMN antibacterial functions.
Purpose of the Study:
- To investigate the effect of the iron chelator deferoxamine on the antibacterial function of PMNs.
- To determine if deferoxamine can protect PMNs from iron-mediated oxidative damage.
- To assess the impact of deferoxamine on bacterial uptake and intracellular killing by PMNs.
Main Methods:
- PMNs were incubated with various concentrations of deferoxamine.
- Bacterial uptake of radiolabeled Staphylococcus aureus was measured.
- Intracellular killing capacity, chemiluminescence, and superoxide production were assessed.
- Experiments included controls with non-incubated PMNs, PMNs incubated without deferoxamine, and PMNs treated with iron-saturated deferoxamine.
Main Results:
- Deferoxamine treatment (1 microM-1 mM) increased Staphylococcus aureus uptake by PMNs by 10%-20% compared to controls.
- This enhancement was not observed with iron-saturated deferoxamine.
- Intracellular killing capacity exceeded 90% for both deferoxamine-treated and control PMNs.
- Deferoxamine-treated PMNs showed enhanced chemiluminescence and superoxide production during phagocytosis.
- PMNs incubated with deferoxamine demonstrated improved bacterial killing capacity.
Conclusions:
- Deferoxamine enhances the antibacterial activity of PMNs.
- This enhancement is likely due to the protection of PMNs against iron-mediated generation of toxic oxygen metabolites.
- Deferoxamine may improve PMN phagocytic function and antibacterial efficacy.