Suppressive Effect of Iron on in vitro Lymphocyte Function: Formation of Iron Polymers as a Possible Explanation

Sóyano, Andrés; Fernandez, Eric; Romano, Egidio

doi:10.1159/000233725

Cited by 8 publications

(4 citation statements)

References 9 publications

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“…Although relatively few studies have investigated the relationship between iron excess and immune function in vivo there is general agreement that increased concentrations of iron are deleterious toT lymphocyte function, natural killer cell (NK) activity and macrophage cytotoxicity./n vitro studies have shown that addition of increasing concentrations of iron inhibit E-rosette formation (44)(45)(46), mitogen-induced proliferation of lymphocytes (PHA and concanavalin A) (47,48), and the mixed lymphocyte reaction (45) and NK cell activity (49).…”

Section: Iron Excess and Immunitymentioning

confidence: 99%

Iron and Immunity

Farthing

1989

Acta Paediatrica

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Farthing, M. J. G. (Department of Gastroenterology, St Bartholomew's Hospital, London, ECIA 7BE, UK). Iron and immunity. Review of animal and human studies concerning the impact of iron deficiency on immune function in vivo indicates that in many instances there is no firm consensus of opinion as to the relationship between iron status and immunity. One major problem with almost all human studies is that other micro‐ and macronutrient deficiencies are inadequately controlled for and thus it is often unclear as to whether reported abnormalities of immune function can be attributed specifically to iron deficiency. Even when abnormalities of immune function have been detected it is often uncertain as to the biological and clinical relevance that these may have for the host. Within these restraints the available studies suggest that iron deficiency may at least contribute to impaired T lymphocyte function as judged by DTH responses in skin and impaired mitogen‐induced proliferation. As in protein energy malnutrition, humoral immunity is largely spared in humans, the balance of evidence suggesting that immunoglobulin production and function is normal, as are serum concentrations of complement. The only other abnormality of non‐specific immunity which has been reported consistently to be abnormal is that of reduced bactericidal activity of polymorphonuclear leucocytes. The clinical relevance of these abnormalities remains to be established. There is, however, no evidence to suggest that individuals with iron deficiency suffer the devastating infective complications of the well defined immunodeficiency syndromes either congenital or acquired. It seems likely therefore that despite the fundamental importance of iron in maintaining the integrity of immune function, humans can tolerate the extremes of deficiency and excess and survive in a relatively healthy state.

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Section: Iron Excess and Immunitymentioning

confidence: 99%

Iron and Immunity

Farthing

1989

Acta Paediatrica

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“…Fernandez (1984) found that ferric citrate inhibited the lymphocyte response to PHA in the presence of 1% serum by 50%, but that at 5% serum and above this inhibition was reduced to less than 20%. In addition, ferric citrate prepared at a 1:1 molar ratio was shown to be more inhibitory than when the ratio of iron to citrate was 1: 20 (Soyano et al 1985b). Such results may be due to the peculiar chemistry of iron.…”

Section: Resultsmentioning

confidence: 91%

“…Iron citrate has been shown to be inhibitory under certain conditions (Bryan and Leech 1983;Soyano et al 1985b) while other iron compounds such as hemoglobin and ferritin have been reported to increase the response of lymphocytes to mitogens in serum-free culture (Tanno et al 1982). It is evident that the effect of iron on the lymphocyte response is very dependent on the conditions of culture, the presence of serum, the type and concentration of mitogen, and the form of iron used.…”

Section: Resultsmentioning

confidence: 99%

Physiological and non-physiological forms of iron affect differently proliferation and ferritin synthesis in human mononuclear cells in vitro.

Taylor¹,

Soyano²,

Romano³

et al. 1987

Tohoku J. Exp. Med.

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The effect of iron in different forms on the proliferative response to mitogen and ferritin content of human mononuclear leukocytes (MNL) was studied in vitro. Iron-loaded transferrin (FeTF) but not apotransferrin (apoTF) significantly enhanced the mitogenic response of MNL in serum-free culture. Removal of TF from serum markedly reduced its effectiveness as a serum supplement. This effect could be almost totally reversed when the serum was reconstituted with both iron and apoTF. Four forms of iron showed a stimulatory effect on ferritin synthesis in MNL in the increasing order : FeTF < iron nitrilotriacetate < iron citrate (molar ratio 1: 20) < iron citrate (1:1). The effect appeared to be correlated with their susceptibility to polymerization in aqueous solution. It is proposed that iron may a) enhance the mitogenic response of MNL, due probably to the physiological form of iron, FeTF, and b) stimulate ferritin synthesis, a protective reaction of the cell to toxic polymerized forms of the metal. lymphocytes ; transferrin ; iron ; ferritin It is well established that alterations of iron balance, particularly deficiency, adversely affect the capacity of humans and experimental animals to effect an immune response, although the underlying mechanisms involved have not been completely clarified . In attempts to understand such effects, the role of iron in cells of the immune system has been evaluated in vitro by measuring the response of lymphocytes to mitogen in the presence or absence of the metal. However, due to the requirement for serum (which contains iron) shown by lymphocytes in culture, results showing the effect of iron addition to such cultures cannot lead to unequivocal conclusions. Results

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“…Possibly, Fe(III)-citrate presumed to form a 1:1 or 1:2 aqueous complex may, in fact, form polynuclear Fe-citrate species (estimated at 72 Å), too large to diffuse into the periplasm (size limit estimated at 13 kDa ≈ 54 Å). Indeed, several studies pointed to the formation of polynuclear Fe(III) species in the presence of citrate at circumneutral pH, when the ratio of [Fe(III)]/[citrate] is close to stoichiometry. ,− The polynuclear species may also be too large to allow full access to the one MtrA solvent-exposed heme, resulting in slower reduction of ΔOMC as compared to WT. Abiotic reduction of Fe(III)-citrate by lysed cells rather than by outer membrane MHCs was ruled out up until 24 h because there was no detectable reduction, and cell viability only started decreasing radically after 24 h (Figure S2A).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Reduction of Aqueous U(V)-dpaea and Solid-Phase U(VI)-dpaea Complexes: The Role of Multiheme c-Type Cytochromes

Molinas

Meibom

Faizova

et al. 2023

Environ. Sci. Technol.

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The biological reduction of soluble U(VI) complexes to form immobile U(IV) species has been proposed to remediate contaminated sites. It is well established that multiheme c-type cytochromes (MHCs) are key mediators of electron transfer to aqueous phase U(VI) complexes for bacteria such as Shewanella oneidensis MR-1. Recent studies have confirmed that the reduction proceeds via a first electron transfer forming pentavalent U(V) species that readily disproportionate. However, in the presence of the stabilizing aminocarboxylate ligand, dpaea 2− (dpaeaH 2 �bis(pyridyl-6-methyl-2-carboxylate)-ethylamine), biologically produced U(V) persisted in aqueous solution at pH 7. We aim to pinpoint the role of MHC in the reduction of U(V)-dpaea and to establish the mechanism of solidphase U(VI)-dpaea reduction. To that end, we investigated U-dpaea reduction by two deletion mutants of S. oneidensis MR-1−one lacking outer membrane MHCs and the other lacking all outer membrane MHCs and a transmembrane MHC−and by the purified outer membrane MHC, MtrC. Our results suggest that solid-phase U(VI)-dpaea is reduced primarily by outer membrane MHCs. Additionally, MtrC can directly transfer electrons to U(V)-dpaea to form U(IV) species but is not strictly necessary, underscoring the primary involvement of outer membrane MHCs in the reduction of this pentavalent U species but not excluding that of periplasmic MHCs.

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Suppressive Effect of Iron on in vitro Lymphocyte Function: Formation of Iron Polymers as a Possible Explanation

Cited by 8 publications

References 9 publications

Iron and Immunity

Iron and Immunity

Physiological and non-physiological forms of iron affect differently proliferation and ferritin synthesis in human mononuclear cells in vitro.

Mechanism of Reduction of Aqueous U(V)-dpaea and Solid-Phase U(VI)-dpaea Complexes: The Role of Multiheme c-Type Cytochromes

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