Desferrioxamine improves neutrophil phagocytosis in thalassemia major

Abstract

The aims of the present study are: first, to assess the toxic role of serum from thalassemic patients in phagocytosis of PMN from healthy controls, and second, to seek to determine whether serum and cellular disturbances of polymorphonuclear neutrophils (PMN) phagocytosis, observed in thalassemic patients, can be prevented and/or corrected by use of desferrioxamine (DFX). Two kinds of in vitro incubations--without or with DFX--were performed. PMN or serum from thalassemic patients or from healthy controls was used. First, a phagocytosis defect of 3 different bacteria species was induced in PMN from healthy controls by incubation in thalassemic serum. Second, DFX could prevent, already at 1 microM, the phagocytic defect induced in normal PMN by the incubation with thalassemic serum, with disappearance of the toxic role of thalassemic serum at higher concentrations. Third, improvement of the phagocytosis defect of PMN from thalassemic patients was also observed at 1 microM of DFX for the 3 bacteria species. Normalization was obtained at higher concentrations for gram-negative bacteria. In vivo studies revealed, after a 3 hr subcutaneous infusion of DFX into 3 thalassemic patients, an improvement of the phagocytosis results and a decrease of the Prussian Blue reactivity of the PMN. It is concluded first that an iron-mediated defect in phagocytosis can be induced in normal neutrophils by incubation in serum from thalassemic patients, and second that a precautious and intensive chelation therapy seems to be advantageous for increasing PMN defense against infectious agents. Special care must nevertheless be taken in order to detect rapidly opportunistic (such as Yersinia) infections.

Decreased Phagolysosomal Fusion of Peripheral Blood Monocytes from Patients with Thalassemia Major

“…In the present study, we demonstrated that the addition of deferoxamine to cell cultures improved phagolysosomal fusion in TM patients. This is in accordance with other authors who showed that deferoxamine, at similar concentrations, en hanced the in vitro phagocytic function of human neutro phils [30,31]. Moreover, Speer et al [32] demonstrated that neutrophil function of children treated with deferox amine was similar to normal controls, suggesting that de feroxamine in vivo could improve neutrophil dysfunction, though they did not include in their study children without chelation therapy.…”

Chronic oxidative stress reduces the respiratory burst response of neutrophils from beta‐thalassaemia patients

“…Our results indicate that thalassaemia PMN contain higher levels of ROS than normal PMN and a lower ability to respond to PMA activation, suggesting an impaired bactericidal activity. The results also show that the oxidants studied, including iron and haemin, which are elevated in the plasma of thalassaemic patients (Cantinieaux et al , 1990), increase the ROS of PMN and reduce the response to PMA by respiratory burst. In contrast, antioxidants reduced ROS, but increased the ability of PMN to response to PMA.…”

“…The mechanism is unclear, but it is possible that one or more components of the ROS generating system is damaged or consumed as a result of the chronic oxidative stress of the cells. We managed to recapitulate this situation in normal PMN by treatment with various oxidants, including iron and haemin, which are known to be high in thalassaemic patients (Cantinieaux et al , 1990). Most of these patients suffer from iron‐overload (in spite of chelation therapy) because of increased dietary iron absorption and frequent therapeutic blood transfusions.…”

Infections in E-β Thalassemia

“…Impairments of phagocyte functions such as chemotaxis, phagocytosis, and intracellular killing have been detected more commonly and consistently than the defects of other host defenses in thalassemia patients (35,38,39). Phagocyte dysfunctions seem to be associated with iron overload (35,38),and their improvement can be demonstrated by desferrioxamine (40).…”