Dataset Information

High mannose N-glycans on red blood cells as phagocytic ligands, mediating both sickle cell anaemia and resistance to malaria

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, expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We found that extravascular haemolysis 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 haemoglobin S. This proteomics analysis is to prove the identify of high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: Aristotelis Antonopoulos

LAB HEAD: Anne Dell

PROVIDER: PXD024022 | Pride | 2021-03-17

REPOSITORIES: Pride

ACCESS DATA

Publications

Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance.

Cao Huan H Antonopoulos Aristotelis A Henderson Sadie S Wassall Heather H Brewin John J Masson Alanna A Shepherd Jenna J Konieczny Gabriela G Patel Bhinal B Williams Maria-Louise ML Davie Adam A Forrester Megan A MA Hall Lindsay L Minter Beverley B Tampakis Dimitris D Moss Michael M Lennon Charlotte C Pickford Wendy W Erwig Lars L Robertson Beverley B Dell Anne A Brown Gordon D GD Wilson Heather M HM Rees David C DC Haslam Stuart M SM Alexandra Rowe J J Barker Robert N RN Vickers Mark A MA

Nature communications 20210319 1

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<sub>5-9</sub>GlcNAc<sub>2</sub>), 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 ...[more]

PMID: 33741926

Similar Datasets

Project description:Various cancers such as colorectal cancer (CRC) are associated with alterations in protein glycosylation. CRC cell lines are frequently used to study these (glyco)biological changes and their mechanisms. However, differences between CRC cell lines with regard to their glycosylation have hitherto been largely neglected. Here, we comprehensively characterized the N-glycan profiles of 25 different CRC cell lines, derived from primary tumors and metastatic sites, in order to investigate their potential as glycobiological tumor model systems and to reveal glycans associated with cell line phenotypes. We applied an optimized, high-throughput membrane-based enzymatic glycan release for small sample amounts. Released glycans were derivatized to stabilize and differentiate between a2,3- and a2,6-linked N-acetylneuraminic acids, followed by N-glycosylation analysis by MALDI-TOF(/TOF)-MS. Our results showed pronounced differences between the N-glycosylation patterns of CRC cell lines. CRC cell line profiles differed from tissue-derived N-glycan profiles with regard to their high-mannose N-glycan content but showed a large overlap for complex type N-glycans, supporting their use as a glycobiological cancer model system. Importantly, we could show that the high-mannose N-glycans did not only occur as intracellular precursors but were also present at the cell surface. The obtained CRC cell line N-glycan features were not clearly correlated with mRNA expression levels of glycosyltransferases, demonstrating the usefulness of performing the structural analysis of glycans. Finally, correlation of CRC cell line glycosylation features with cancer cell markers and phenotypes revealed an association between highly fucosylated glycans and CDX1 and/or villin mRNA expression that both correlate with cell differentiation. Together, our findings provide new insights into CRC-associated glycan changes and setting the basis for more in-depth experiments on glycan function and regulation.

Dataset Information

High mannose N-glycans on red blood cells as phagocytic ligands, mediating both sickle cell anaemia and resistance to malaria

Publications

Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure