Document Detail

Anchorage on fibronectin via VLA-5 (alpha5beta1 integrin) protects rheumatoid synovial cells from Fas-induced apoptosis.
MedLine Citation:
PMID:  16249227     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Rheumatoid synovial cells are resistant to apoptosis induction in vivo, whereas, fibroblast-like synovial cells in rheumatoid arthritis (RA-FLS) are vulnerable to Fas-induced apoptosis in vitro.
OBJECTIVE: To clarify this discrepancy by studying the contribution of the interaction between cellular integrin and matrix fibronectin (Fn), which is significantly increased in the rheumatoid joints, to the induction of apoptosis in RA-FLS.
METHODS: Integrin and Fas mRNAs were measured by reverse transcription-polymerase chain reaction in RA-FLS. Integrins expressed in rheumatoid synovial tissues were analysed by immunohistochemistry. RA-FLS plated either on Fn or on control poly-L-lysine were incubated with agonistic anti-Fas monoclonal antibodies (mAbs). Apoptosis induction was evaluated using terminal deoxynucleotidyl transferase mediated UTP nick end labelling (TUNEL) and immunoblotting for caspase-3 and poly (ADP-ribose) polymerase in the presence or absence of anti-VLA-5 mAb.
RESULTS: VLA-5 (alpha5beta1 integrin), a major integrin expressed on RA-FLS, was required for the adhesion of RA-FLS on Fn. RA-FLS plated on Fn were more resistant to Fas-induced apoptosis than those plated on control poly-L-lysine. This protection by Fn was reversed by anti-VLA-5 mAb.
CONCLUSION: Anchorage of RA-FLS on matrix Fn via VLA-5 protects RA-FLS from Fas-induced apoptosis, and Fn abundantly present in rheumatoid synovium appears to afford RA-FLS resistance against apoptosis induction in vivo.
A Kitagawa; Y Miura; R Saura; M Mitani; H Ishikawa; A Hashiramoto; S Yoshiya; S Shiozawa; M Kurosaka
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Publication Detail:
Type:  Journal Article     Date:  2005-10-25
Journal Detail:
Title:  Annals of the rheumatic diseases     Volume:  65     ISSN:  0003-4967     ISO Abbreviation:  Ann. Rheum. Dis.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-15     Completed Date:  2006-06-12     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0372355     Medline TA:  Ann Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  721-7     Citation Subset:  IM    
Department of Orthopaedic Surgery, Kobe University School of Medicine, Japan.
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MeSH Terms
Antibodies, Monoclonal / pharmacology
Antigens, CD95 / metabolism*
Apoptosis* / immunology
Arthritis, Rheumatoid / metabolism*,  pathology
Biological Markers / analysis
Caspase 3
Caspases / analysis
Cell Adhesion
Cells, Cultured
Collagen Type XI / analysis
Fibroblasts / metabolism,  pathology
Fibronectins / metabolism*
Immunoblotting / methods
Immunohistochemistry / methods
In Situ Nick-End Labeling
Integrin alpha5beta1 / immunology,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Statistics, Nonparametric
Synovial Membrane / metabolism*,  pathology
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD95; 0/Biological Markers; 0/COL11A2 protein, human; 0/Collagen Type XI; 0/Fibronectins; 0/Integrin alpha5beta1; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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