The Macrophage: A Cellular Factory at the Interphase Between Iron and Immunity for the Control of Infections

Theurl, Igor; Fritsche, Gernot; Ludwiczek, Susanne; Garimorth, Katja; Bellmann‐Weiler, Rosa; Weiss, Günter

doi:10.1007/s10534-005-3710-1

Cited by 67 publications

(44 citation statements)

References 101 publications

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“…The low level of TIBC found in ovariectomized rats is unusual because when serum iron decreases and cellular iron demand is high, the TIBC level usually increases. The atypical scenario that we have found is compatible with a chronic inflammatory condition, in which iron release from cells decreases, lowering the level of TIBC [38], as may occur in certain type of iron deficiency related to inflammation and /or liver disease, two common patho-physiological conditions associated with menopause or ovariectomy [39]. A linkage between E 2 serum level and iron metabolism disturbances has been described not only in reference to hypoestrogenism, such as, occurs following ovariectomy or in menopause, but also during pregnancy, a condition in which E 2 is elevated [40].…”

Section: Discussionsupporting

confidence: 61%

Ovariectomy and estrogen treatment modulate iron metabolism in rat adipose tissue

Raso

Irace

Esposito

et al. 2009

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 30A c c e p t e d M a n u s c r i p Graphical AbstractPage 2 of 30 A c c e p t e d M a n u s c r i p t E-mail address: rsantama@unina.it (R. Santamaria). * ManuscriptPage 3 of 30 A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 ABSTRACTIron is essential for many biological processes and its deficiency or excess is involved in pathological conditions. At cellular level, the maintenance of iron homeostasis is largely accomplished by the transferrin receptor (TfR)-1 and by ferritin, whose expression is mainly regulated post-transcriptionally by Iron Regulatory Proteins (IRPs).This study examines the hypothesis that modification of serum estrogen levels by ovariectomy and 17β-estradiol (E 2 ) treatment in rats modulate serum iron-status parameters and iron metabolism in adipose tissue. In particular, we evaluated the RNA binding of IRP1 by electrophoretic mobility shift assay and IRP1, ferritin, and TfR-1 expression in adipose tissue by Western blot analysis.Ovariectomy, besides a lowered serum iron and transferrin iron binding capacity, remarkably decreased the binding activity of IRP1 in peritoneal and subcutaneous adipose tissues, and these effects were reversed by E 2 treatment. Moreover, ovariectomy determined a decrease of IRP1 expression, which was significant in subcutaneous adipose tissue. Consistent with IRP1 regulation, an increase of ferritin and a decrease of TfR-1 expression were observed in peritoneal adipose tissue from ovariectomized animals, while the treatment with E 2 reconstituted TfR-1 level. A similar expression profile of TfR-1 was observed in subcutaneous adipose tissue, where ferritin level did not change in ovariectomized animals, and was increased after E 2 treatment.Our results indicate that estrogen level changes can regulate the binding activity of the IRP1, and consequently ferritin and TfR-1 expression in adipose tissue, suggesting a relationship among serum and tissue iron parameters, estrogen status and adiposity.

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Section: Discussionsupporting

confidence: 61%

Ovariectomy and estrogen treatment modulate iron metabolism in rat adipose tissue

Raso

Irace

Esposito

et al. 2009

Biochemical Pharmacology

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“…Cytokines enhance iron storage by inducing ferritin synthesis and erythrophagocytosis due to up-regulation of iron importer and reducing iron exporter molecules (43). Additional inflammation-dependent restriction of iron is achieved by increase of transferrin saturation, as well as by PMN granule release of lipocalin and lactoferrin (43,44).…”

Section: Discussionmentioning

confidence: 99%

Lipoproteins in Staphylococcus aureus Mediate Inflammation by TLR2 and Iron-Dependent Growth In Vivo

Schmaler

Jann

Ferracin

et al. 2009

The Journal of Immunology

105

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“…32 Indeed, iron deficiency results in lower infections and skewing toward Th1 immune responses, whereas susceptibility to bacterial infections increases with increased iron concentration. 33 However, iron loading of macrophages inhibits IFN-␥-mediated secretion of proinflammatory cytokines, reduces expression of MHC II and indoleamine-2,3 dioxygenase, and impairs NO synthesis, all of which are consistent with a compromised phagocytic and microbicidal macrophage activity and a shift toward Th2 effector functions. 33 It would therefore appear that the iron-loaded macrophages are switched from a proinflammatory toward an anti-inflammatory alternatively activated (M2) state, which is thought to be associated with the resolution of inflammation.…”

Section: Ironmentioning

confidence: 94%

“…33 However, iron loading of macrophages inhibits IFN-␥-mediated secretion of proinflammatory cytokines, reduces expression of MHC II and indoleamine-2,3 dioxygenase, and impairs NO synthesis, all of which are consistent with a compromised phagocytic and microbicidal macrophage activity and a shift toward Th2 effector functions. 33 It would therefore appear that the iron-loaded macrophages are switched from a proinflammatory toward an anti-inflammatory alternatively activated (M2) state, which is thought to be associated with the resolution of inflammation. 16 Interestingly, M2 macrophages, unlike their M1 counterparts, have been demonstrated to actively export non-hemeassociated iron.…”

Section: Ironmentioning

confidence: 94%

Immunoregulatory Effects of Stored Red Blood Cells

2011

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Some clinical studies have identified potential adverse patient outcomes associated with RBC storage length. This may in part be due to the release of potentially hazardous bioactive products that accumulate during storage and are delivered at high concentrations during transfusion. In this situation, a proinflammatory tissue microenvironment may be established that can alter immunoregulatory mechanisms. This review highlights some of the potential immunomodulatory effects of stored RBCs that may be responsible for adverse transfusion reactions.

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The Macrophage: A Cellular Factory at the Interphase Between Iron and Immunity for the Control of Infections

Cited by 67 publications

References 101 publications

Ovariectomy and estrogen treatment modulate iron metabolism in rat adipose tissue

Ovariectomy and estrogen treatment modulate iron metabolism in rat adipose tissue

Lipoproteins in Staphylococcus aureus Mediate Inflammation by TLR2 and Iron-Dependent Growth In Vivo

Immunoregulatory Effects of Stored Red Blood Cells

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