Structure of upregulated VLA-4 antigen expressed on PBL from SLE

在SLE合并血管炎患者中，已证实不仅LFA-1的表达上调，而且vla4的表达也上调。此外，在合并血管炎的SLE中发现了180 kD的额外高分子量带迁移，而在正常个体和无血管炎的SLE中发现了140 kD的正常vla4。SLE伴血管炎患者外周血T细胞对纤维连接蛋白和VCAM-1的粘附功能和信号转导升高。在粘附VLA-4配体后，在这些T细胞中观察到ca内流，这表明这将信号引入细胞内部。在SLE合并血管炎中，通过功能激活的vla4进行信号转导。接下来，我们研究了在这些患者中，通过vla4进行信号转导的分子相互作用，这些患者的表达和功能都上调。考虑到整合素通过与细胞骨架蛋白结合并形成黏附来传递信号的证据，利用共聚焦光学系统的贴壁细胞分析系统（ACAS）对整合素β -中国细胞质结构域结合的细胞骨架蛋白talin进行了观察。我们发现未受刺激的SLE T细胞在纤维连接蛋白上有局灶性粘附和talin的表达，而正常T细胞则没有。同时，在这些局灶性粘连周围发现了强烈的酪氨酸磷酸化，这表明这些通过整合素的信号转导途径在SLE合并血管炎的T细胞中被功能性激活并强烈表达。

Structure of VLA-4 antigen expressed on SLE T cellsIn patients with SLE complicated with vasculitis, it has been demonstrated that expressions of not only LFA-1, but also VLA-4 were upregulated. Moreover, the additional high molecular weight band migrating at 180 kD of VLA-4 was obaerved in SLE with vasculitis, whereas 140 kD normal VLA-4 was detected in normal individual and SLE without vasculitis.Adhesion function and signal transduction via VLA-4 in SLE with vasculitisPeripheral T cells frpm SLE with vasculitis showed elevated adherence to fibronectin and VCAM-1. After adhesito VLA-4 ligands, ca influx was observed in these T cells, suggesting that this elicited the signal into the cell interior.Signal transduction through functionally activated VLA-4 in SLE with vasculitisWe next examined the molecular interaction of signal transduction through VLA-4 in these fn these patients in which expression as well as function was upregulated. Given the evidences that intgrins trnasmit signals by binding to cytoskeltal proteins and forming mocal adhesion, talin, one of these cytoskeltal proteins which can binds to cytoplasmic domain of integrin beta chian were observed by Adherent Cell Analyzing System (ACAS) equipped with confocal optical system. We found that focal adhesion and the expression of talin were observed of unstimulated SLE T cells adhered onto fibronectin, whereas those of normal T cells were not. At same time, strong tyrosine-phosphorylation was noted adaround those focal adhesions, suggesting that these signal transduction pathways through intgrins were functionally activated and strongly expressed in T cells from SLE with vasculitis.