Mannose receptor interacts with Fc receptors and is critical for the development of crescentic glomerulonephritis in mice.

2.50
Hdl Handle:
http://hdl.handle.net/10547/228933
Title:
Mannose receptor interacts with Fc receptors and is critical for the development of crescentic glomerulonephritis in mice.
Authors:
Chavele, Konstantia-Maria; Martinez-Pomares, Luisa; Domin, Jan; Pemberton, Samantha; Haslam, Stuart M.; Dell, Anne; Cook, H. Terence; Pusey, Charles D.; Gordon, Siamon; Salama, Alan D.
Abstract:
Crescentic glomerulonephritis (CGN), which frequently results in acute and chronic kidney disease, is characterized by and dependent on glomerular infiltration by macrophages. The mannose receptor (MR) is a pattern recognition receptor implicated in the uptake of endogenous and microbial ligands by macrophages, mesangial cells (MCs), and selected endothelial cells. It is upregulated on alternatively activated macrophages (i.e., macrophages associated with tissue repair and humoral immunity) and involved in antigen presentation to T cells. We used the mouse model of nephrotoxic nephritis to investigate the role of MR in CGN. Our results demonstrate what we believe to be a novel role for MR in the promotion of CGN that is independent of adaptive immune responses. MR-deficient (Mr-/-) mice were protected from CGN despite generating humoral and T cell responses similar to those of WT mice, but they demonstrated diminished macrophage and MC Fc receptor-mediated (FcR-mediated) functions, including phagocytosis and Fc-mediated oxygen burst activity. Mr-/- MCs demonstrated augmented apoptosis compared with WT cells, and this was associated with diminished Akt phosphorylation. Macrophage interaction with apoptotic MCs induced a noninflammatory phenotype that was more marked in Mr-/- macrophages than in WT macrophages. Our results demonstrate that MR augments Fc-mediated function and promotes MC survival. We suggest that targeting MR may provide an alternative therapeutic approach in CGN while minimizing the impact on adaptive immune responses, which are affected by conventional immunosuppressive approaches.
Affiliation:
Renal Section, Department of Medicine, Imperial College London, UK
Citation:
Mannose receptor interacts with Fc receptors and is critical for the development of crescentic glomerulonephritis in mice. 2010, 120 (5):1469-1478 J. Clin. Invest.
Publisher:
American Society for Clinical Investigation
Journal:
The Journal of clinical investigation
Issue Date:
May-2010
URI:
http://hdl.handle.net/10547/228933
DOI:
10.1172/JCI41560
PubMed ID:
20407205
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/20407205
Type:
Article
Language:
en
ISSN:
1558-8238
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorChavele, Konstantia-Mariaen_GB
dc.contributor.authorMartinez-Pomares, Luisaen_GB
dc.contributor.authorDomin, Janen_GB
dc.contributor.authorPemberton, Samanthaen_GB
dc.contributor.authorHaslam, Stuart M.en_GB
dc.contributor.authorDell, Anneen_GB
dc.contributor.authorCook, H. Terenceen_GB
dc.contributor.authorPusey, Charles D.en_GB
dc.contributor.authorGordon, Siamonen_GB
dc.contributor.authorSalama, Alan D.en_GB
dc.date.accessioned2012-06-14T10:46:43Z-
dc.date.available2012-06-14T10:46:43Z-
dc.date.issued2010-05-
dc.identifier.citationMannose receptor interacts with Fc receptors and is critical for the development of crescentic glomerulonephritis in mice. 2010, 120 (5):1469-1478 J. Clin. Invest.en_GB
dc.identifier.issn1558-8238-
dc.identifier.pmid20407205-
dc.identifier.doi10.1172/JCI41560-
dc.identifier.urihttp://hdl.handle.net/10547/228933-
dc.description.abstractCrescentic glomerulonephritis (CGN), which frequently results in acute and chronic kidney disease, is characterized by and dependent on glomerular infiltration by macrophages. The mannose receptor (MR) is a pattern recognition receptor implicated in the uptake of endogenous and microbial ligands by macrophages, mesangial cells (MCs), and selected endothelial cells. It is upregulated on alternatively activated macrophages (i.e., macrophages associated with tissue repair and humoral immunity) and involved in antigen presentation to T cells. We used the mouse model of nephrotoxic nephritis to investigate the role of MR in CGN. Our results demonstrate what we believe to be a novel role for MR in the promotion of CGN that is independent of adaptive immune responses. MR-deficient (Mr-/-) mice were protected from CGN despite generating humoral and T cell responses similar to those of WT mice, but they demonstrated diminished macrophage and MC Fc receptor-mediated (FcR-mediated) functions, including phagocytosis and Fc-mediated oxygen burst activity. Mr-/- MCs demonstrated augmented apoptosis compared with WT cells, and this was associated with diminished Akt phosphorylation. Macrophage interaction with apoptotic MCs induced a noninflammatory phenotype that was more marked in Mr-/- macrophages than in WT macrophages. Our results demonstrate that MR augments Fc-mediated function and promotes MC survival. We suggest that targeting MR may provide an alternative therapeutic approach in CGN while minimizing the impact on adaptive immune responses, which are affected by conventional immunosuppressive approaches.en_GB
dc.language.isoenen
dc.publisherAmerican Society for Clinical Investigationen_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/20407205en_GB
dc.rightsArchived with thanks to The Journal of clinical investigationen_GB
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshFemale-
dc.subject.meshGene Expression Regulation-
dc.subject.meshGlomerulonephritis-
dc.subject.meshLectins, C-Type-
dc.subject.meshMacrophages-
dc.subject.meshMale-
dc.subject.meshMannose-Binding Lectins-
dc.subject.meshMesangial Cells-
dc.subject.meshMice-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Transgenic-
dc.subject.meshModels, Biological-
dc.subject.meshOxygen-
dc.subject.meshPhagocytosis-
dc.subject.meshPhosphorylation-
dc.subject.meshReceptors, Cell Surface-
dc.subject.meshReceptors, Fc-
dc.subject.meshT-Lymphocytes-
dc.titleMannose receptor interacts with Fc receptors and is critical for the development of crescentic glomerulonephritis in mice.en
dc.typeArticleen
dc.contributor.departmentRenal Section, Department of Medicine, Imperial College London, UKen_GB
dc.identifier.journalThe Journal of clinical investigationen_GB
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