Iron metabolism during infection and neoplasia

Letendre, Elaine D.

doi:10.1007/bf00047608

Cited by 16 publications

(6 citation statements)

References 90 publications

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“…Serum iron levels may be decreased in conditions besides iron deficiency; the most frequent is probably the anemia associated with chronic conditions such as uremia and inflammation (40 -42). Hypoferremia (i.e., low serum iron; not to be confused with hypoferritinemia) is observed during inflammation, neoplasia, trauma, myocardial infarction, surgery, and stressful conditions (41). Hence, our found association between low serum iron (Ͻ50 g/ml) and increased death risk may be due to inflammation.…”

Section: Discussionmentioning

confidence: 53%

Time-Dependent Associations between Iron and Mortality in Hemodialysis Patients

Kalantar-Zadeh¹,

Regidor²,

McAllister³

et al. 2005

Journal of the American Society of Nephrology

265

261

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The independent association between the indices of iron stores or administered intravenous iron, both of which vary over time, and survival in patients who are on maintenance hemodialysis (MHD) is not clear. It was hypothesized that the observed associations between moderately high levels of three iron markers (serum ferritin, iron, and iron saturation ratio) or administered intravenous iron and all-cause and cardiovascular death is due to the time-varying confounding effect of malnutrition-inflammation-cachexia syndrome (MICS). Time-dependent Cox regression models were examined using prospectively collected data of the 2-yr (July 2001 to June 2003) historical cohort of 58,058 MHD patients from virtually all DaVita dialysis clinics in the United States. After time-dependent and multivariate adjustment for case mix, administered intravenous iron and erythropoietin doses, and available surrogates of MICS, serum ferritin levels between 200 and 1200 ng/ml (reference 100 to 199 ng/ml), serum iron levels between 60 and 120 g/ml (reference 50 to 59 g/ml), and iron saturation ratio between 30 and 50% (reference 45 to 50%) were associated with the lowest all-cause and cardiovascular death risks. Compared with those who did not receive intravenous iron, administered intravenous iron up to 400 mg/mo was associated with improved survival, whereas doses >400 mg/mo tended to be associated with higher death rates. The association between serum ferritin levels >800 ng/ml and mortality in MHD patients seems to be due mostly to the confounding effects of MICS. I n patients who are on maintenance hemodialysis (MHD), markers of anemia, including low blood hemoglobin concentrations, are associated with poor clinical outcomes (1,2). Consequently, management of anemia by recombinant human erythropoietin (EPO) by increasing serum hemoglobin toward the target of 11.0 to 12.0 g/dl is reported consistently to improve outcome measures in MHD patients (3-6). However, much controversy exists with regard to the association between measures of iron stores or changes in these values by iron administration and clinical outcome in these individuals (7). Although in the pre-EPO era iron overload was a major cause of morbidity in MHD patients, its significance in the post-EPO era remains unclear. A recent observational study in 1283 MHD patients indicated that a low, rather than a high, baseline serum iron quartile was associated with increased mortality and hospitalization over 12 mo of observation (8). Even though quartile analysis enables us to uncover nonlinear relationships, large sample sizes with repeated measures are needed to compare the mortality predictability of smaller increments of iron markers. Moreover, the association between other iron markers and survival remains to be determined.Many observational studies have examined the association between a baseline laboratory value at the start of the cohort and the survival and ignored variations in clinical and laboratory measures over time. It is not clear whether longitudinal changes in...

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Section: Discussionmentioning

confidence: 53%

Time-Dependent Associations between Iron and Mortality in Hemodialysis Patients

Kalantar-Zadeh¹,

Regidor²,

McAllister³

et al. 2005

Journal of the American Society of Nephrology

265

261

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“…From this step the two models diverge; in the redox model, before the transferrin-transferrin receptor complex becomes trapped within endocytic vesicles, the concerted action of protons and reducing equivalents (2) furnished by the NADH: ferricyanide oxidoreductase in close proximity to the transferrin receptor evokes the destabilization of the transferrin-iron bond (3) and the reduction if iron (4). The ferrous iron is bound by a membrane binder/carrier specific for Fe2" (5). Iron is then translocated across the membrane to the cytosolic side (6) where it is picked up by cytosolic iron acceptors (7).…”

Section: Thorstensen Unpublished Work)mentioning

confidence: 99%

“…In this review we attempt to summarize the new knowledge and controversies encountered during the last [4][5] years. The focus is on iron metabolism by the hepatocyte.…”

Section: Introductionmentioning

confidence: 99%

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The role of transferrin in the mechanism of cellular iron uptake

Thorstensen

Romslo

1990

Biochemical Journal

187

106

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INTRODUCTIONThe role of transferrin and its cell surface receptor in cellular iron metabolism has received considerable interest during the last decade. Hence, over this period several reviews covering various aspects of the topic have been published.In this review we attempt to summarize the new knowledge and controversies encountered during the last 4-5 years. The focus is on iron metabolism by the hepatocyte. We also view the concept of transferrin-cell interactions from angles which previously may not have been given particular attention, and we include some aspects of iron metabolism not normally covered by reviews of this type. Central parts of what may be regarded as well-established knowledge either have been entirely omitted, or are only briefly described or mentioned to the extent considered relevant to the particular topic discussed. Important aspects of iron metabolism such as iron adsorption, haemochromatosis, ferritin iron and iron in infection and neoplasia are not covered in the present paper. Instead, the reader is referred to one or more of the recently published reviews [1-5] and references therein.

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“…However, Zhao et al . [ 55 ] noted growth of wild-type meningococcal strains on 30–50 μg/ml free Hb and so it is not clear if the availability of free Hb was a determinant of the inability of tbp mutants to replicate in whole blood, The discrepancy may arise from the fact that the whole blood model only mimics the early stages of an infection where iron-loaded Tf is abundant [ 56 , 57 ]. Thus the TbpBA receptor may be sufficient for growth of meningococci during the early stages of disease.…”

Section: Discussionmentioning

confidence: 99%

Investigation into the Antigenic Properties and Contributions to Growth in Blood of the Meningococcal Haemoglobin Receptors, HpuAB and HmbR

et al. 2015

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Acquisition of iron from host complexes is mediated by four surface-located receptors of Neisseria meningitidis. The HmbR protein and heterodimeric HpuAB complex bind to haemoglobin whilst TbpBA and LbpBA bind iron-loaded transferrin and lactoferrin complexes, respectively. The haemoglobin receptors are unevenly distributed; disease-causing meningococcal isolates encode HmbR or both receptors while strains with only HpuAB are rarely-associated with disease. Both these receptors are subject to phase variation and 70–90% of disease isolates have one or both of these receptors in an ON expression state. The surface-expression, ubiquity and association with disease indicate that these receptors could be potential virulence factors and vaccine targets. To test for a requirement during disease, an hmbR deletion mutant was constructed in a strain (MC58) lacking HpuAB and in both a wild-type and TbpBA deletion background. The hmbR mutant exhibited an identical growth pattern to wild-type in whole blood from healthy human donors whereas growth of the tbpBA mutant was impaired. These results suggest that transferrin is the major source of iron for N. meningitidis during replication in healthy human blood. To examine immune responses, polyclonal antisera were raised against His-tagged purified-recombinant variants of HmbR, HpuA and HpuB in mice using monolipopolysaccharide as an adjuvant. Additionally, monoclonal antibodies were raised against outer membrane loops of HmbR presented on the surface of EspA, an E. coli fimbrial protein. All antisera exhibited specific reactivity in Western blots but HmbR and HpuA polyclonal sera were reactive against intact meningococcal cells. None of the sera exhibited bactericidal activity against iron-induced wild-type meningococci. These findings suggest that the HmbR protein is not required during the early stages of disease and that immune responses against these receptors may not be protective.

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Iron metabolism during infection and neoplasia

Cited by 16 publications

References 90 publications

Time-Dependent Associations between Iron and Mortality in Hemodialysis Patients

Time-Dependent Associations between Iron and Mortality in Hemodialysis Patients

The role of transferrin in the mechanism of cellular iron uptake

Investigation into the Antigenic Properties and Contributions to Growth in Blood of the Meningococcal Haemoglobin Receptors, HpuAB and HmbR

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