| Extracellular calreticulin is present in the joints of patients with rheumatoid arthritis and inhibits FasL (CD95L)-mediated apoptosis of T cells. | |
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MedLine Citation:
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PMID: 20533543 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The binding of FasL (CD95L) to its receptor, Fas (CD95), induces apoptosis. Studies have shown that in patients with rheumatoid arthritis (RA), T lymphocytes are resistant to FasL-induced apoptosis in vivo but are susceptible to FasL-induced apoptosis in vitro. Dysfunction in this mechanism may be an important contributor to the pathophysiology of RA. Thus, the present study was undertaken to determine which factors might inhibit FasL-Fas binding in vivo and those that would inhibit apoptosis of T lymphocytes in an in vitro model system. METHODS: Human Jurkat T cells rendered apoptotic by FasL exposure were analyzed by flow cytometry. Necrosis was determined according to measurement of lactate dehydrogenase release. Quantification of calreticulin in plasma and synovial fluid and of calreticulin-FasL binding was performed by enzyme-linked immunosorbent assay. Measurement of nitrite/nitrate in the plasma and synovial fluid was carried out by chemiluminescence assay. RESULTS: Extracellular calreticulin was present at a significantly higher concentration in the plasma (median 10.3 ng/ml, interquartile range [IQR] 14.8 ng/ml) and synovial fluid (median 10.3 ng/ml, IQR 12.0 ng/ml) of RA patients (each P < 0.05) compared with the plasma (median 3.1 ng/ml, IQR 1.3 ng/ml) and synovial fluid (median 2.9 ng/ml, IQR 0.9 ng/ml) of patients with psoriatic arthritis and the plasma of healthy control subjects (median 2.9 ng/ml, IQR 0.9 ng/ml). Calreticulin concentrations in the synovial fluid correlated with the tender and swollen joint counts and the activity scores on the 28-joint Disease Activity Score assessment. Calreticulin also bound directly to FasL. In vitro, calreticulin (2-16 ng/ml) inhibited FasL-induced apoptosis of Jurkat T cells. CONCLUSION: Calreticulin was present at higher concentrations in the plasma and synovial fluid of RA patients. Calreticulin had the capacity to bind directly to FasL and to inhibit FasL-mediated apoptosis of Jurkat T cells, and thus might play a role in inhibiting apoptosis of inflammatory T cells in RA. |
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Authors:
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Joanna M Tarr; Paul G Winyard; Brent Ryan; Lorna W Harries; Richard Haigh; Nick Viner; Paul Eggleton |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arthritis and rheumatism Volume: 62 ISSN: 1529-0131 ISO Abbreviation: Arthritis Rheum. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-08 Completed Date: 2010-11-23 Revised Date: 2011-12-01 |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
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Languages: eng Pagination: 2919-29 Citation Subset: AIM; IM |
Affiliation:
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Peninsula College of Medicine and Dentistry, and University of Exeter, Exeter, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Aged, 80 and over Apoptosis / immunology* Arthritis, Rheumatoid / immunology* Calreticulin / blood, immunology* Case-Control Studies Fas Ligand Protein / physiology* Female Humans Jurkat Cells Male Middle Aged Severity of Illness Index Synovial Fluid / immunology* T-Lymphocytes / physiology |
| Grant Support | |
ID/Acronym/Agency:
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//Arthritis Research UK |
| Chemical | |
Reg. No./Substance:
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0/Calreticulin; 0/Fas Ligand Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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