Comment Concerning the Role of CD47 and Signal Regulatory Protein Alpha in Regulating the Clearance of Aged Red Blood Cells

Lutz, Hans

doi:10.1159/000350507

Cited by 3 publications

(2 citation statements)

References 18 publications

(17 reference statements)

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“…Recently, it has been reported that experimental aging of erythrocytes induces a conformational change in CD47 (39). However, the mechanism proposed to explain CD47 involvement in clearance of experimental RBC aging is unclear (50). Plasmodium infection may induce a form of accelerated RBC aging by the generation of reactive oxygen species that oxidize RBC hemoglobin to hemichrome.…”

Section: Discussionmentioning

confidence: 99%

CD47-SIRPα Interactions Regulate Macrophage Uptake of Plasmodium falciparum-Infected Erythrocytes and Clearance of Malaria In Vivo

Ayi

Serghides

et al. 2016

Infect Immun

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Macrophages can recognize altered cell surface ligands on aged, malignant, or infected cells, triggering their phagocytic uptake. CD47 is a glycoprotein "marker of self" that is expressed on cell membranes in humans and mice (1, 2). Decreased levels of CD47 are present on senescent and apoptotic cells and are associated with increased macrophage clearance. Conversely, high levels of CD47 expressed on cancer cells and leukemic stem cells may prevent the cells from being efficiently cleared in vivo (2, 3).CD47 exerts its inhibitory effect on phagocytosis through its interaction with macrophage signal-regulatory protein alpha (SIRP␣). SIRP␣ and CD47 constitute a cell-cell communication system that plays essential roles in hematopoietic and immunological regulation. Following CD47 engagement, SIRP␣ cytoplasmic-region immunoreceptor tyrosine-based inhibitory motifs (ITIMs) recruit Src homology-2 domain-containing protein tyrosine phosphatases SHP-1 and SHP-2, resulting in decreased macrophage uptake and reduced production of proinflammatory mediators (2, 4-7). A critical role of CD47-SIRP␣ signaling in negatively regulating erythrophagocytosis has been demonstrated by the rapid macrophage clearance of CD47-deficient red blood cells (RBCs) when transfused into wild-type animals (2).CD47 has been implicated in mediating the outcome of several infectious processes. CD47-deficient mice succumb to bacterial peritonitis (8) but are less susceptible to Staphylococcus aureusinduced arthritis (9) and are protected from lipopolysaccharide (LPS)-induced acute lung injury and Escherichia coli pneumonia (10). SIRP␣ is polymorphic and highly expressed on hepatic Kupffer cells and splenic red pulp macrophages, cell populations important in the innate control of malaria (11,12). A recent study of Plasmodium yoelii malaria in a nonlethal murine model reported that CD47 was an important determinant of age-specific RBC invasion and parasite burden (13). Although Plasmodium falciparum is responsible for the majority of cases of severe and cerebral malaria (CM), the role of CD47-SIRP␣ in falciparum malaria has not been reported. In this study, we used a combined genetic and functional approach to investigate the contribution of CD47-SIRP␣ interactions to innate clearance of P. falciparuminfected RBCs in vitro and in a lethal model of experimental cerebral malaria (ECM). We show that CD47 on infected RBCs and SIRP␣ on macrophages are important determinants of the outcome in vivo and of macrophage phagocytosis of P. falciparuminfected RBCs in vitro. A direct role for SIRP␣ was established by functional disruption of receptor signaling using anti-SIRP␣ antibodies and recombinant SIRP␣-Fc fusion proteins.

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Section: Discussionmentioning

confidence: 99%

CD47-SIRPα Interactions Regulate Macrophage Uptake of Plasmodium falciparum-Infected Erythrocytes and Clearance of Malaria In Vivo

Ayi

Serghides

et al. 2016

Infect Immun

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“…The authors think that RBC aging induces a conformational change in CD47 whereby it binds thrombospondin-1 and then interacts with SIRPα and induces phagocytosis of aged RBC. The evidence is weak, because the required concentration of the thrombospondin-1 peptide exceeded the thrombospondin-1 concentration in plasma by 10 3 –10 4 (Lutz, 2013 ) and the phenomena had been studied on RBC that (a) were not actively leucocyte-depleted and (b) were oxidatively damaged by CuSO 4 and ascorbic acid rather than in vivo aged.…”

Section: Other Clearance Mechanismsmentioning

confidence: 99%

Mechanisms tagging senescent red blood cells for clearance in healthy humans

2013

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This review focuses on the analysis and evaluation of the diverse senescence markers suggested to prime red blood cells (RBC) for clearance in humans. These tags develop in the course of biochemical and structural alterations accompanying RBC aging, as the decrease of activities of multiple enzymes, the gradual accumulation of oxidative damage, the loss of membrane in form of microvesicles, the redistribution of ions and alterations in cell volume, density, and deformability. The actual tags represent the penultimate galactosyl residues, revealed by desialylation of glycophorins, or the aggregates of the anion exchanger (band 3 protein) to which anti-galactose antibodies bind in the first and anti-band 3 naturally occurring antibodies (NAbs) in the second case. While anti-band 3 NAbs bind to the carbohydrate-free portion of band 3 aggregates in healthy humans, induced anti-lactoferrin antibodies bind to the carbohydrate-containing portion of band 3 and along with anti-band 3 NAbs may accelerated clearance of senescent RBC in patients with anti-neutrophil cytoplasmic antibodies (ANCA). Exoplasmically accessible phosphatidylserine (PS) and the alterations in the interplay between CD47 on RBC and its receptor on macrophages, signal regulatory protein alpha (SIRPalpha protein), were also reported to induce erythrocyte clearance. We discuss the relevance of each mechanism and analyze the strength of the data.

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Red Blood Cell Inspired Strategies for Drug Delivery: Emerging Concepts and New Advances

et al. 2022

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Comment Concerning the Role of CD47 and Signal Regulatory Protein Alpha in Regulating the Clearance of Aged Red Blood Cells

Cited by 3 publications

References 18 publications

CD47-SIRPα Interactions Regulate Macrophage Uptake of Plasmodium falciparum-Infected Erythrocytes and Clearance of Malaria In Vivo

CD47-SIRPα Interactions Regulate Macrophage Uptake of Plasmodium falciparum-Infected Erythrocytes and Clearance of Malaria In Vivo

Mechanisms tagging senescent red blood cells for clearance in healthy humans

Red Blood Cell Inspired Strategies for Drug Delivery: Emerging Concepts and New Advances

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