Treatment of human bone marrow with recombinant placenta immunoregulator ferritin results in myelopoiesis and T-cell suppression through modulation of the cytokine-chemokine networks

Moroz, Chaya; Grunspan, Anna; Zahalka, Muayad A.; Traub, Leonid; Kodman, Yona; Yaniv, Isaac

doi:10.1016/j.exphem.2005.10.006

Cited by 14 publications

(12 citation statements)

References 23 publications

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“…Ferritin was described as a signaling molecule [30], immune regulator in humans [31] and that H-ferritin chain (PLIF: placenta immunomodulator ferritin) suppresses myelopoiesis and T cell by modulating the cytokine-chemokine network [32]. These findings reveal a new insight in increased serum ferritin values in lung cancer patients.…”

Section: Discussionmentioning

confidence: 96%

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer

et al. 2009

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The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.

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Section: Discussionmentioning

confidence: 96%

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer

et al. 2009

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“…These data indicating that H-ferritin has an immunosuppressive function (Fig. 1) have been recently supported by evidence that another ferritin-like molecule has similar inhibitory functions insofar as a cloned human chimeric H-ferritin chain (PLIF: placenta immunomodulator ferritin) suppresses myelopoiesis and T cells by modulating the cytokineechemokine network [14].…”

Section: Ferritin As An Immune Regulatormentioning

confidence: 90%

New functions for an iron storage protein: The role of ferritin in immunity and autoimmunity

Recalcati

Invernizzi

Arosio

et al. 2008

Journal of Autoimmunity

229

168

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“…Furthermore, regarding structural aspects it has to be noted, that the 43 kDa ferritin subunit contained in p43‐PLF is supposed to represent a dimer of PLIF, a novel 22 kDa ferritin H‐chain homologue containing a novel 48 amino acid C‐terminus (C48; Moroz et al, 2002) which by itself (recombinant C48) exerts immunosuppressive activities (Moroz et al, 2002, 2006; Weinberger et al, 2003; Zahalka et al, 2003). Similarly, the 43 kDa ferritin subunit detectable in immunosuppressive melanoma‐derived H‐chain ferritin also has been identified as a dimer of a 21.5 kDa ferritin H‐chain (Gray et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Since antibodies raised against the 43 kDa subunit of p43‐PLF immunologically also crossreact with PLIF, and both ferritins share similar immunomodulatory properties it has been concluded that p43‐PLF represents a PLIF dimer (Moroz et al, 2002). Interestingly, recombinant C48 has been shown to exhibit immunomodulatory activities, in particular mediating cytokine‐chemokine interactions, stimulation of IL‐10 production in monocytes and inhibition of T‐cell proliferation (Weinberger et al, 2003; Zahalka et al, 2003; Moroz et al, 2006). Moreover, the immunomodulatory properties of the 43 kDa subunit‐bearing melanoma‐derived H‐chain ferritin have also been shown to be IL‐10 dependent (Gray et al, 2001).…”

mentioning

confidence: 99%

Ferritin—a mediator of apoptosis?

Bresgen¹,

Ohlenschläger²,

Fiedler³

et al. 2007

Journal Cellular Physiology

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Previously we have demonstrated an apoptosis inducing activity for a rat hepatocyte conditioned medium (CM) presumably mediated by acidic isoferritins. Here, we present support for this assumption since isoferritins purified from different rat hepatocyte CM significantly enhanced the frequency of apoptotic cells in primary rat hepatocytes, an effect completely inhibited by a neutralizing anti-H-ferritin antibody. The apoptosis induction appears to be related to a 43 kDa ferritin subunit contained in the isoferritins released from primary hepatocytes, presumably representing a ferritin heavy/light chain heterodimer. In addition, these isoferritins immunologically crossreact with antibodies raised against placental isoferritin p43-PLF (which also contains a 43 kDa ferritin subunit) and melanoma-derived H-chain ferritin, representing ferritin isoforms which reveal immunomodulatory properties. Furthermore, p53 and FasL are upregulated upon isoferritin treatment in a time dependent mode, and apoptosis induction can be suppressed by neutralizing anti-FasL antibodies. Proapoptotic Bid is upregulated too and translocated into mitochondria in primary hepatocytes exposed to the isoferritins purified from the CM. Finally, epidermal growth factor (EGF) and dexamethasone (DEX), which counteract proapoptotic mitochondrial signalling, almost completely abolished the proapoptotic effect of the hepatocyte derived isoferritins. In conclusion, our findings demonstrate that acidic isoferritins with homology to immunomodulatory ferritin isoforms (p43-PLF, melanoma-derived-H-chain ferritin) are released from hepatocytes in vitro, and are able to stimulate upregulation of p53 and mediate apoptosis involving Fas (CD95) signalling as well as addressing the intrinsic mitochondrial proapoptotic pathway.

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Treatment of human bone marrow with recombinant placenta immunoregulator ferritin results in myelopoiesis and T-cell suppression through modulation of the cytokine-chemokine networks

Cited by 14 publications

References 23 publications

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer

Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer

New functions for an iron storage protein: The role of ferritin in immunity and autoimmunity

Ferritin—a mediator of apoptosis?

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