Red blood cell phagocytosis and lysis following oxidative damage by phenylhydrazine

Magnani, Mauro; Stocchi, Vilberto; Cucchiarini, Luigi; Chiarantini, Laura; Fornaini, G

doi:10.1002/cbf.290040406

Cited by 23 publications

(10 citation statements)

References 31 publications

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“…Reduced RBC life span and number in CRF have been frequently discussed in connection with redox state mod ifications [4-6, 11, 19], Furthermore it has been demon strated that the uremic RBC displays several metabolic al terations [27,28], reduced cellular deformability [29], modified electrolyte composition and water content [30,31]. These alterations are similar to those observed after free-radical exposure and can explain the higher suscepti bility to hemolysis observed in uremic subjects [15,[32][33][34], Oxidative damage accelerates RBC aging, inducing he molysis through lipid peroxidation and protein damage [33,34], Glutathione levels in uremic patients vary in different studies, probably as a consequence of the methodology and patient heterogeneity. Mimic-Oka et al [16] and we [17] did not observe any modification of RBC-GSH levels in HD patients.…”

Section: Discussionsupporting

confidence: 66%

Erythrocyte Redox State in Uremic Anemia: Effects of Hemodialysis and Relevance of Glutathione Metabolism

et al. 1994

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Reduced and oxidized glutathione and pyridine coenzymes, glutathione-related enzymes and CuZn-superoxide dismutase (CuZn-SOD) were investigated in the RBC of patients with chronic renal failure (CRF) and in age- and sex-matched controls. The effects of hemodialysis (HD) were also studied. A defective RBC redox state was shown in the CRF group based on a decreased GSH/GSSG ratio and NADPH levels. Increased activities of glutathione transferase (GSH-S-T) and CuZn-SOD were observed before HD. Dialysis apparently restores the levels of antioxidant enzymes and at the same time strongly affects the redox state. Thus we can speculate that HD can generate severe redox impairment inducing damage in RBC and plasma antioxidant enzymes. Increased erythrocyte GSSG and GSM-S-T levels coupled with a reduced hexose monophosphate shunt (HMPS) function may be useful indexes of oxidative stress in uremic anemia.

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Section: Discussionsupporting

confidence: 66%

Erythrocyte Redox State in Uremic Anemia: Effects of Hemodialysis and Relevance of Glutathione Metabolism

et al. 1994

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“…To further ascertain that CD47 phenotype is a determinant of malaria infectivity, we investigated the effect of induced generation of young RBC on the outcome of GFP-PyNL infection in the WT C57BL/6 mice. Phenyl hydrazine (PHZ), a known anemia inducer, causes oxidative damage to the RBC, followed by cell lysis that leads to the generation of new RBC to maintain the homeostasis (18). After two consecutive injections of PHZ in the WT mice, the packed cell volume of RBC dropped significantly (60.4 ± 1.2% before PHZ treatment vs. 30.5 ± 4.2% after PHZ treatment; Fig.…”

Section: Modulation Of Cd47 Expression Affects the Parasite Burden Anmentioning

confidence: 99%

CD47 regulates the phagocytic clearance and replication of thePlasmodium yoeliimalaria parasite

Banerjee

Khandelwal

Kozakai

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Several Plasmodium species exhibit a strong age-based preference for the red blood cells (RBC) they infect, which in turn is a major determinant of disease severity and pathogenesis. The molecular basis underlying this age constraint on the use of RBC and its influence on parasite burden is poorly understood. CD47 is a marker of self on most cells, including RBC, which, in conjunction with signal regulatory protein alpha (expressed on macrophages), prevents the clearance of cells by the immune system. In this report, we have investigated the role of CD47 on the growth and survival of nonlethal Plasmodium yoelii 17XNL (PyNL) malaria in C57BL/6 mice. By using a quantitative biotin-labeling procedure and a GFP-expressing parasite, we demonstrate that PyNL parasites preferentially infect high levels of CD47 (CD47hi)-expressing young RBC. Importantly, C57BL/6 CD47−/− mice were highly resistant to PyNL infection and developed a 9.3-fold lower peak parasitemia than their wild-type (WT) counterparts. The enhanced resistance to malaria observed in CD47−/− mice was associated with a higher percentage of splenic F4/80+ cells, and these cells had a higher percentage of phagocytized parasitized RBC than infected WT mice during the acute phase of infection, when parasitemia was rapidly rising. Furthermore, injection of CD47-neutralizing antibody caused a significant reduction in parasite burden in WT C57BL/6 mice. Together, these results strongly suggest that CD47hi young RBC may provide a shield to the malaria parasite from clearance by the phagocytic cells, which may be an immune escape mechanism used by Plasmodium parasites that preferentially infect young RBC.

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“…To test the hypothesis that rapid posttransfusion clearance contributes to the increased immunogenicity of stored murine RBCs, we induced rapid posttransfusion clearance of fresh RBCs by chemical or heat treatment. Phenylhydrazine induces RBC oxidant stress, leading to rapid posttransfusion clearance by the reticuloendothelial system (RES) 25‐27 . Heat treatment (50°C for 30 min) damages RBCs in an oxidant stress–independent manner, also leading to rapid post‐transfusion clearance 28,29 .…”

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confidence: 99%

Rapid clearance of transfused murine red blood cells is associated with recipient cytokine storm and enhanced alloimmunogenicity

et al. 2011

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Background 14-day stored RBCs containing an RBC specific transgenic antigen (HOD) induce a recipient pro-inflammatory cytokine storm and are significantly more immunogenic compared to fresh RBCs. Given that recipient mice clear transfused stored RBCs more rapidly than fresh RBCs, we hypothesized that rapid RBC clearance was associated with adverse transfusion outcomes. Study Design and Methods HOD RBCs were treated by two distinct methodologies known to lead to rapid post-transfusion RBC clearance: phenylhydrazine or heat. HOD antigen expression was analyzed on the treated cells prior to transfusion, and RBC recovery, recipient cytokine response, and recipient anti-HOD alloimmunization response were measured post-transfusion. Results Phenylhydrazine and heat treatment each led to near complete RBC clearance in recipients by 24 hours post-transfusion, without significantly altering HOD antigen expression on the transfused RBCs. Recipients of phenylhydrazine or heat-treated RBCs had elevated circulating levels of KC/CXCL-1, MCP-1, and IL-6 following transfusion. Furthermore, phenylhydrazine or heat treated RBCs were significantly more immunogenic than control RBCs, with a mean 25.1-fold enhancement and 10.3 fold enhancement, respectively, of anti-HOD alloimmunization magnitude by flow cytometric crossmatch. Conclusions Three separate insults to RBCs (storage, phenylhydrazine, or heat treatment) result in rapid post-transfusion clearance, with a recipient pro-inflammatory cytokine storm and enhanced alloimmunogenicity. These data are consistent with the hypothesis that rapid clearance of RBCs is causally involved in these outcomes, and suggest that human donor RBCs with favorable post-transfusion clearance profiles may be less immunogenic.

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Red blood cell phagocytosis and lysis following oxidative damage by phenylhydrazine

Cited by 23 publications

References 31 publications

Erythrocyte Redox State in Uremic Anemia: Effects of Hemodialysis and Relevance of Glutathione Metabolism

Erythrocyte Redox State in Uremic Anemia: Effects of Hemodialysis and Relevance of Glutathione Metabolism

CD47 regulates the phagocytic clearance and replication of thePlasmodium yoeliimalaria parasite

Rapid clearance of transfused murine red blood cells is associated with recipient cytokine storm and enhanced alloimmunogenicity

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