Document Detail


Mannose receptor interacts with Fc receptors and is critical for the development of crescentic glomerulonephritis in mice.
MedLine Citation:
PMID:  20407205     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Konstantia-Maria Chavele; Luisa Martinez-Pomares; Jan Domin; Samantha Pemberton; Stuart M Haslam; Anne Dell; H Terence Cook; Charles D Pusey; Siamon Gordon; Alan D Salama
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-19
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  120     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-04     Completed Date:  2010-05-20     Revised Date:  2012-02-07    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1469-78     Citation Subset:  AIM; IM    
Affiliation:
Renal Section, Division of Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Female
Gene Expression Regulation*
Glomerulonephritis / metabolism*
Lectins, C-Type / metabolism*
Macrophages / metabolism
Male
Mannose-Binding Lectins / metabolism*
Mesangial Cells / metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Models, Biological
Oxygen / metabolism
Phagocytosis
Phosphorylation
Receptors, Cell Surface / metabolism*
Receptors, Fc / metabolism*
T-Lymphocytes / metabolism
Grant Support
ID/Acronym/Agency:
B19088//Biotechnology and Biological Sciences Research Council; BBF0083091//Biotechnology and Biological Sciences Research Council; //Medical Research Council
Chemical
Reg. No./Substance:
0/Lectins, C-Type; 0/Mannose-Binding Lectins; 0/Receptors, Cell Surface; 0/Receptors, Fc; 0/mannose receptor; 7782-44-7/Oxygen
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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