Anchorage on fibronectin via VLA-5 (α5β1 integrin) protects rheumatoid synovial cells from Fas-induced apoptosis
Anchorage on fibronectin via VLA-5 (α5β1 integrin) protects rheumatoid synovial cells from Fas-induced apoptosis
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DOI：
10.1136/ard.2005.041707
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发表时间：
2006-06-01
影响因子：
27.4
通讯作者：
Kurosaka, M.
中科院分区：
文献类型：
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作者：
Kitagawa, A.;Miura, Y.;Kurosaka, M.
背景：类风湿关节炎(RA-FLS)滑膜细胞在体内不能诱导凋亡，而成纤维细胞样滑膜细胞(RA-FLS)在体外易受Fas诱导的凋亡。目的：通过研究类风湿关节中细胞整合素和基质纤维连接蛋白(FN)的相互作用在诱导RA-FLS细胞凋亡中的作用，阐明这一差异。免疫组织化学方法检测类风湿滑膜组织中整合素的表达。将RA-FLS分别接种于FN和对照组的多聚L赖氨酸上，与激动型抗Fas单抗孵育。用末端脱氧核苷酸转移酶介导的UTP缺口末端标记法(TUNEL)和免疫印迹法检测抗VLA-5单抗对Caspase-3和聚ADP-核糖聚合酶的诱导作用。结果：RA-FLS表达的主要整合素VLA-5(α5-β1整合素)参与了RA-FLS与FN的黏附。FN表面的RA-FLS对Fas诱导的细胞凋亡的抵抗力强于对照组的多聚L赖氨酸。结论：通过VLA-5将RA-FLS锚定在基质FN上，可保护RA-FLS免受Fas诱导的细胞凋亡，类风湿滑膜中大量存在的FN可在体内抵抗RA-FLS诱导的细胞凋亡。
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 (alpha 5 beta 1 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.