Hromadnikova Ilona, Nguyen Thi Thu Hien, Zlacka Denisa, Sedlackova Lucie, Popelka Stanislav, Veigl David, Pech Jan, Vavrincova Pavla, Sosna Antonin
Department of Molecular Biology and Cell Pathology, 3rd Medical Faculty, Charles University, Ruska 87, Prague 10, 10000, Czech Republic.
Rheumatol Int. 2008 Jul;28(9):837-44. doi: 10.1007/s00296-008-0532-9. Epub 2008 Jan 30.
We examined the membrane expression of inducible Hsp70 and HSP receptors like TLR2, TLR4, CD14, CD36, CD40 and CD91 on fibroblast-like synovial cells (SC) derived from synovial tissue in 23 patients with rheumatoid arthritis (RA), who underwent synovectomy by using flow cytometric analysis. For comparison, autologous skin fibroblasts (SF) derived from the operation wound were tested. Significantly higher Hsp70 expression was found on synovial cells than on skin fibroblasts (median SC 21.4% x SF 5.0%, P < 0.001). Both synovial cells and skin fibroblasts expressed high levels of cell surface CD91 (median SC 80.2% x SF 79.2%), however, no or low levels of CD14, CD40, TLR2, TLR4 and CD36. Further, we observed high co-expression of CD91 and Hsp70 on RA synovial cells (median 18.6%), while skin fibroblasts showed only background Hsp70 expression (median 3.9%, P < 0.001). Since we demonstrated the high prevalence of inducible Hsp70 in RA synovial fluids, we speculate that Hsp70 might be captured onto the membrane of synovial cells from the extracellular space via the CD91 receptor. The significance of the Hsp70 interaction with synovial cells via CD91 remains undefined, but may mediate other non-immune purposes.
我们采用流式细胞术分析,检测了23例类风湿关节炎(RA)患者滑膜组织来源的成纤维样滑膜细胞(SC)上诱导型Hsp70以及HSP受体如TLR2、TLR4、CD14、CD36、CD40和CD91的膜表达情况。作为对照,检测了手术伤口处的自体皮肤成纤维细胞(SF)。结果发现,滑膜细胞上的Hsp70表达显著高于皮肤成纤维细胞(滑膜细胞中位数为21.4%,皮肤成纤维细胞为5.0%,P < 0.001)。滑膜细胞和皮肤成纤维细胞均高表达细胞表面CD91(滑膜细胞中位数为80.2%,皮肤成纤维细胞为79.2%),然而,CD14、CD40、TLR2、TLR4和CD36表达缺失或水平较低。此外,我们观察到RA滑膜细胞上CD91和Hsp70共表达水平较高(中位数为18.6%),而皮肤成纤维细胞仅呈现背景性Hsp70表达(中位数为3.9%,P < 0.001)。由于我们已证实RA滑膜液中诱导型Hsp70的高发生率,我们推测Hsp70可能通过CD91受体从细胞外空间捕获到滑膜细胞膜上。Hsp70通过CD91与滑膜细胞相互作用的意义尚不清楚,但可能介导其他非免疫目的。