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Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance.
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- Author(s): Cao H;Cao H; Antonopoulos A; Antonopoulos A; Henderson S; Henderson S; Wassall H; Wassall H; Brewin J; Brewin J; Masson A; Masson A; Shepherd J; Shepherd J; Konieczny G; Konieczny G; Patel B; Patel B; Williams ML; Williams ML; Davie A; Davie A; Forrester MA; Forrester MA; Hall L; Hall L; Minter B; Minter B; Tampakis D; Tampakis D; Moss M; Moss M; Lennon C; Lennon C; Pickford W; Pickford W; Erwig L; Erwig L; Robertson B; Robertson B; Dell A; Dell A; Brown GD; Brown GD; Brown GD; Wilson HM; Wilson HM; Rees DC; Rees DC; Haslam SM; Haslam SM; Alexandra Rowe J; Alexandra Rowe J; Barker RN; Barker RN; Vickers MA; Vickers MA; Vickers MA; Vickers MA
- Source:
Nature communications [Nat Commun] 2021 Mar 19; Vol. 12 (1), pp. 1792. Date of Electronic Publication: 2021 Mar 19.- Publication Type:
Journal Article; Research Support, Non-U.S. Gov't- Language:
English - Source:
- Additional Information
- Source: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
- Publication Information: Original Publication: [London] : Nature Pub. Group
- Subject Terms: Anemia, Sickle Cell/*metabolism ; Erythrocytes/*metabolism ; Mannose/*metabolism ; Phagocytes/*metabolism ; Polysaccharides/*metabolism; Erythrocyte Membrane/metabolism ; Erythrocyte Membrane/parasitology ; Erythrocytes/parasitology ; Flow Cytometry/methods ; Hemolysis ; Humans ; Ligands ; Malaria, Falciparum/metabolism ; Malaria, Falciparum/parasitology ; Membrane Glycoproteins/metabolism ; Phagocytosis ; Plasmodium falciparum/physiology ; Protein Binding ; Receptors, Immunologic/metabolism
- Abstract: In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (Man
5-9 GlcNAc2 ), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait. - References: Mediterr J Hematol Infect Dis. 2012;4(1):e2012065. (PMID: 23170194)
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J Proteome Res. 2007 Aug;6(8):3242-55. (PMID: 17585793) - Grant Information: BB/F008309/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; 082098 United Kingdom WT_ Wellcome Trust; BBF0083091 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; 102705 United Kingdom WT_ Wellcome Trust; 094847 United Kingdom WT_ Wellcome Trust; MR/N006364/1 United Kingdom MRC_ Medical Research Council; BBK0161641 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; United Kingdom WT_ Wellcome Trust; 97377 United Kingdom WT_ Wellcome Trust; 102705/Z/13/Z United Kingdom WT_ Wellcome Trust
- Accession Number: 0 (Ligands)
0 (MRC1 protein, human)
0 (Membrane Glycoproteins)
0 (Polysaccharides)
0 (Receptors, Immunologic)
PHA4727WTP (Mannose) - Publication Date: Date Created: 20210320 Date Completed: 20210405 Latest Revision: 20230216
- Publication Date: 20240105
- Accession Number: PMC7979802
- Accession Number: 10.1038/s41467-021-21814-z
- Accession Number: 33741926
- Source:
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