Deferoxamine enhances phagocytic function of human polymorphonuclear leukocytes

Asbeck, BS van; Jj, Marx; Struyvenberg, A; Kats, JH van; Verhoef, J

doi:10.1182/blood.v63.3.714.bloodjournal633714

Cited by 10 publications

(14 citation statements)

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“…Incubation of PMN from healthy controls in normal serum containing increasing DFX concentrations induces progressive alteration of phagocytosis performance. Our results are at variance with those obtained by Van Asbeck et al [ 5 ] ; this is possibly due to the fact that these authors performed the incubations in the absence of serum. The reasons for the phagocytosis defect induced by DFX in our experiments are unknown.…”

Section: Discussioncontrasting

confidence: 97%

“…In iron overload, the PMN phagocytosis defect may be due to an overstimulation of the Haber-Weiss reaction leading to an excess production of oxidant radicals, particularly the hydroxyl radical [4]. The latter is a potent oxidizing agent capable of inducing a membrane lesion and a secondary phagocytosis defect [ 5 ] . Alternatively, direct toxicity of iron (11) or of an iron (11)-oxygen intermediate on the cell membrane has been recently suggested [2].…”

Section: Introductionmentioning

confidence: 99%

“…Alternatively, direct toxicity of iron (11) or of an iron (11)-oxygen intermediate on the cell membrane has been recently suggested [2]. Desferrioxamine (DFX) has been shown to favor the phagocytosis of normal or in vitro iron %intoxicated PMN [2,5]. Its action has notably been attributed to a possible inhibition of oxidant radical production by a decrease in the iron available for the Haber-Weiss reaction or for direct toxicity to the membrane [2].…”

Section: Introductionmentioning

confidence: 99%

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Desferrioxamine improves neutrophil phagocytosis in thalassemia major

et al. 1990

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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.

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Section: Discussioncontrasting

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Desferrioxamine improves neutrophil phagocytosis in thalassemia major

et al. 1990

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“…In patients with an iron overload, there seem to be at least three factors causing the increased susceptibility to infections (5)(6)(7)(8)(9): firstly, the decreased concentration of the bacteriostatic, non-iron saturated, host-binding proteins such as transferrin and lactoferrin; secondly, the magnified virulence of the pathogens induced by the increased iron availability; and thirdly, abnormalities of monocytes and PMN functions. Recent studies, conducted in vitro and in vivo by Van Asbeck et a1 (10)(11)(12)(13) as well as by our group (14,15) have indeed demonstrated the toxic effect of excess iron on PMN phagocytosis.…”

mentioning

confidence: 61%

Neutrophil dysfunctions in thalassaemia major: The role of cell iron overload

Cantinieaux

Hariga

Ferster³

et al. 1987

European J of Haematology

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The susceptibility to infections was recorded in 13 patients with I3 thalassaemia major (T.P.). The following parameters were also investigated in their polymorphonuclear neutrophils (PMN): nitro blue tetrazolium (NBT) reduction, heated yeast and Escherichia coli phagocytosis, Escherichia coli killing and myeloperoxydase activity. These results were compared to those obtained in healthy controls (H.C.). The Perk's reaction was performed on PMN and graded according to a scoring system with the aim of quantifying the iron intoxication of PMN. Phagocytosis and Perk's reaction of PMN from H.C. were also studied after 20 h of incubation with thalassaemic serum. 6 T.P. out of 13 developed septicaemia during their lifetime and in all 9 septicaemic episodes were noted. Phagocytosis was greatly impaired, disclosing both cellular and serum abnormalities. The mean percentage of Perk's positive PMN was 13% in T.P., contrasting with the constant negative reaction in H.C. The incubation of PMN from H.C. with serum from T.P. induced the simultaneous appearance of a phagocytosis defect and of a positive Perl's reaction. It was concluded that in I3 thalassaemia major the phagocytosis of PMN was altered due to a combination of serum and cellular abnormalities and that both may be related to the iron overload.

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“…Some investigations have presented that DFO mediates enhancement of polymorphonuclear leukocytes (PMN) function (van Asbeck et al, 1984) and reduces tissue injury as well as lethality in LPS-treated mice (Vulcano et al, 2000). Moreover, local infusion of DFO, not systemically administered, has demonstrated the effectiveness in tissue protection and anti-inflammation (Lauzon et al, 2006;Hanson et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

In vitro activity of deferoxamine against Porphyromonas gingivalis

Moon¹,

Herr²,

Kim

et al. 2011

FEMS Microbiol Lett

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Deferoxamine (DFO), an FDA-approved iron chelator used for treatment of iron poisoning, affects bacteria as iron availability is intimately connected with growth and several virulence determinants. However, little is known about the effect on oral pathogens. In this study, the effect of DFO on Porphyromonas gingivalis, a major periodontopathogen which has an essential growth requirement for hemin (Fe(3+)-protoporphyrin IX), was evaluated. The viability of P. gingivalis W83 was not affected by 0.06-0.24 mM DFO, whereas the doubling time of the bacterium was considerably prolonged by DFO. The inhibitory effect was evident at earlier stages of growth and reduced by supplemental iron. UV-visible spectra using the pigments from P. gingivalis cells grown on blood agar showed that DFO inhibited μ-oxo bisheme formation by the bacterium. DFO decreased accumulation and energy-driven uptake of hemin by P. gingivalis. Antibacterial effect of H(2)O(2) and metronidazole against P. gingivalis increased in the presence of DFO. Collectively, DFO is effective for hemin deprivation in P. gingivalis suppressing the growth and increasing the susceptibility of the bacterium to other antimicrobial agents such as H(2)O(2) and metronidazole. Further experiments are necessary to show that DFO may be used as a therapeutic agent for periodontal disease.

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Deferoxamine enhances phagocytic function of human polymorphonuclear leukocytes

Cited by 10 publications

References 0 publications

Desferrioxamine improves neutrophil phagocytosis in thalassemia major

Desferrioxamine improves neutrophil phagocytosis in thalassemia major

Neutrophil dysfunctions in thalassaemia major: The role of cell iron overload

In vitro activity of deferoxamine against Porphyromonas gingivalis

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