Document Detail

Mesangial matrix-activated monocytes express functional scavenger receptors and accumulate intracellular lipid.
MedLine Citation:
PMID:  18281317     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Monocyte recruitment into the mesangium and foam cell formation are recognized features of glomerular injury. External signals encountered by infiltrating mononuclear cells may determine their behaviour and thereby potentially influence disease outcome. Having previously demonstrated that monocytes are activated by exposure to matrix secreted by mesangial cells, we set out to determine whether matrix activation of monocytes led to expression of a macrophage phenotype. METHODS: THP-1 mononuclear cells were incubated for up to 120 h (5 days) with 500 microg/ml solublized matrix extracted from cultured human mesangial cells or with phorbol myristate ester (PMA-positive control) or albumin (negative control). Expression of peroxisome proliferator activated receptor-gamma (PPAR-gamma) and of scavenger receptors was used as a marker of monocyte to macrophage differentiation. The presence of functional scavenger receptors was examined by assessing cellular uptake of Dil-labelled acetylated (Ac)-LDL by flow cytometry. Matrix-mediated LDL oxidation was assessed using agarose gel electrophoresis to determine mobility shifts. RESULTS: Matrix activation was associated with an increase in the expression of PPAR-gamma, scavenger receptor-B (CD36) and scavenger receptor-A mRNA with a corresponding increase in PPAR-gamma protein. Matrix-activated cells incubated with Ac-LDL demonstrated foam cell formation, whilst incubation with Dil-labelled Ac-LDL led to an increase in mean fluorescence intensity of 373 +/- 34.8% (P < 0.005) as compared to albumin (100%) and PMA (423 +/- 55.8%) (P < 0.005). This could be inhibited by the addition of excess unlabelled ligand, suggesting specific involvement of scavenger receptors. Incubation of LDL with mesangial matrix in the absence of mesangial cells or monocytes led to enhanced electrophoretic mobility of the recovered lipoprotein on agarose gel, an effect that could be inhibited by the addition of anti-oxidants. CONCLUSION: Exposure to mesangial cell matrix induces expression of monocyte characteristics associated with a macrophage phenotype and promotes oxidation of LDL, thereby converting this lipoprotein to a scavenger receptor ligand. These observations may help to explain foam cell formation in the mesangium in the context of glomerular disease.
Enam U Rahman; Xiong Z Ruan; Ravinder S Chana; Nigel J Brunskill; James Gaya; Stephen H Powis; Zac Varghese; John F Moorhead; David C Wheeler
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Publication Detail:
Type:  Journal Article     Date:  2008-02-14
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  23     ISSN:  1460-2385     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2008 Jun 
Date Detail:
Created Date:  2008-05-21     Completed Date:  2008-07-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  England    
Other Details:
Languages:  eng     Pagination:  1876-85     Citation Subset:  IM    
Centre for Nephrology, Royal Free and University College Medical School, Hampstead Campus, Rowland Hill Street, London NW3 2PF, UK.
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MeSH Terms
Antigens, CD36 / genetics,  metabolism
Base Sequence
Biological Markers / metabolism
Blotting, Western
Cell Movement
Cells, Cultured
Flow Cytometry
Foam Cells / cytology,  metabolism*
Gene Expression Regulation
Glomerular Mesangium / cytology,  physiology*
Intracellular Fluid / metabolism
Lipid Peroxidation / physiology*
Molecular Sequence Data
Monocytes / physiology*
RNA, Messenger / analysis
Receptors, Scavenger / genetics,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Statistics, Nonparametric
Reg. No./Substance:
0/Antigens, CD36; 0/Biological Markers; 0/RNA, Messenger; 0/Receptors, Scavenger

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

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