Upregulation of Interleukin-10 and Inhibition of Alloantigen Responses by Transferrin and Transferrin-Derived Glycans

Lesnikova, Marina; Lesnikov, Vladimir; Arrighi, S.; Kistler, Gonzague S.; Pierpaoli, Walter; Deeg, H. Joachim

doi:10.1089/15258160050079498

Cited by 11 publications

(6 citation statements)

References 58 publications

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“…We confirmed those data in a canine model [57]. In vitro experiments showed that Tf, particularly in the form of ApoTf, suppressed alloreactivity as well as mitogen-induced proliferation [39,58,59], and had profound anti-apoptotic effects. For example, in non-transformed murine (NMH) and human (HH4) hepatocyte cell lines, Fas-mediated apoptosis was down-modulated or prevented by ApoTf [60].…”

Section: Introductionsupporting

confidence: 83%

Iron overload, hematopoietic cell transplantation, and graft-versus-host disease

Deeg

Spaulding

Shulman

2009

Leukemia & Lymphoma

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Many patients who undergo hematopoietic cell transplantation (HCT) present with anemia and have received red blood cell transfusions before HCT. As a result, iron overload is frequent and appears to be particularly prominent in patients with myelodysplastic syndromes (MDS). There is evidence that peritransplant events contribute to further iron accumulation, although the mechanism that disrupts normal iron homeostasis remains to be determined. Recent studies suggest that iron overload, as determined by ferritin levels, a surrogate marker for iron, is a risk factor for increased non-relapse mortality after HCT. Iron overload is associated with an increased rate of infections, in particular with fungal organisms. Furthermore. anecdotal data suggest that increased hepatic iron may mimic the clinical picture of (chronic) graft-versus-host-disease (GVHD). Whether excess iron contributes to GVHD and whether iron depletion, be it by phlebotomy or chelation, reduces the posttransplantation complication rate and improves transplant outcome has yet to be determined.

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Section: Introductionsupporting

confidence: 83%

Iron overload, hematopoietic cell transplantation, and graft-versus-host disease

Deeg

Spaulding

Shulman

2009

Leukemia & Lymphoma

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“…[1][2][3] Recent data from several laboratories suggest, however, that the role of Tf is not restricted to this well recognized function, and that Tf exerts profound effects on cellular cytokine profiles, cell/cell interactions and cell integrity. [4][5][6][7] For example, Tf interferes with programmed cell death induced via agonistic Fas signals, TNF-alpha and gamma-irradiation. 5,8 Liver cells express high levels of Fas, and Fas-mediated apoptosis is one mechanism of liver failure.…”

Section: Introductionmentioning

confidence: 99%

Protection of human and murine hepatocytes against Fas-induced death by transferrin and iron

et al. 2006

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Recent studies in a murine model show that transferrin (Tf) interferes with Fas-mediated hepatocyte death and liver failure by decreasing pro-apoptotic and increasing anti-apoptotic signals. We show here in vitro in murine and human hepatocyte cell lines and in vivo in mice that Fas-induced apoptosis is modulated by exogenous Tf and iron. The results obtained with iron-free Tf (ApoTf), iron-saturated Tf (FeTf), and the iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH) in its iron-free and iron-saturated (FeSIH) forms indicate that apoptosis-modulating effects of Tf are not mediated by iron alone. Both the Tf molecule and iron affect multiple aspects of cell death, and the route of iron delivery to the cell may be critical for the final outcome of cellular Fas signaling. Survival of hepatocytes 'stressed' by Fas signals can be manipulated by Tf and iron and may be a target for prophylactic and therapeutic interventions.

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“…Surprisingly, however, blockade of TfR1 by a neutralizing antibody did not prevent the anti-apoptotic effect of Tf [16,17]. We speculated that TfR2 [9,18] might mediate the anti-apoptotic effects of Tf.…”

Section: Resultsmentioning

confidence: 99%

Transferrin fails to provide protection against Fas-induced hepatic injury in mice with deletion of functional transferrin-receptor type 2

et al. 2008

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We reported previously that Fas-induced hepatic failure in normal mice was attenuated or prevented by exogenous transferrin (Tf), particularly apoTf. Here we show in C57BL6J/129 mice with genetic inactivation of transferrin receptor 2 (TfR2 Y245X ), that Fas-induced hepatotoxicity (apoptosis; rise in plasma aspartate aminotransferase (AST) levels) was comparable to that in wild-type mice, but was not modified by pretreatment with Tf. Rises in plasma AST were preceded by a decline in serum iron levels. AST elevations and iron declines were more profound in female than in male mice. Female mice also showed higher baseline levels of Bcl-xL in hepatocytes, which declined significantly upon treatment with agonistic anti-Fas antibody. These data confirm the cytoprotective function of Tf, and show a novel property of TfR2. Both apoptotic Fas responses and cytoprotective effects of Tf were associated with significant shifts in plasma iron levels, which quantitatively differed between male and female mice.

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Upregulation of Interleukin-10 and Inhibition of Alloantigen Responses by Transferrin and Transferrin-Derived Glycans

Cited by 11 publications

References 58 publications

Iron overload, hematopoietic cell transplantation, and graft-versus-host disease

Iron overload, hematopoietic cell transplantation, and graft-versus-host disease

Protection of human and murine hepatocytes against Fas-induced death by transferrin and iron

Transferrin fails to provide protection against Fas-induced hepatic injury in mice with deletion of functional transferrin-receptor type 2

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