Yang Y-H, Huang Y-H, Lin Y-L, Wang L-C, Chuang Y-H, Yu H-H, Lin Y-T, Chiang B-L
Department of Paediatrics, National Taiwan University Hospital, College of Medicine, National Taiwan University, 7 Chung-Shan South Road, Taipei, Taiwan.
Clin Exp Immunol. 2006 May;144(2):247-53. doi: 10.1111/j.1365-2249.2006.03076.x.
Recently, sera from children with active Henoch-Schönlein purpura (HSP) have been found to enhance interleukin (IL)-8 production by human umbilical venous endothelial cells (HUVEC). To further determine the possible factor with the ability to enhance endothelial IL-8 production in sera from acute stage of HSP, 10 children with HSP at the acute stage and 10 healthy controls were enrolled. IgA antiendothelial cell antibodies (AECA) were detected by cell-based ELISA. Active sera with or without pretreatment with anti-human IgA antibody, sera of controls, and immunoglobulin A (IgA) derived from sera were used to stimulate the HUVEC. The ability of these factors to enhance endothelial IL-8 production was evaluated. Furthermore, signalling pathways were also assayed by different inhibitors, and confirmed by immunoblotting. Serum levels of IgA AECA in HPS patients at the acute stage were significantly higher than in controls (P < 0.001). The active sera could enhance endothelial IL-8 production (P = 0.004, compared with control sera), and the ability of these sera was mostly abolished when pretreated with fixed anti-human IgA antibody. The supernatant IL-8 levels of endothelial cells stimulated by IgA derived from acute stage of HSP were statistically higher than controls (P < 0.001). PD98059, an inhibitor of ERK phosphorylation, significantly reduced IgA AECA-stimulated endothelial IL-8. IgA AECA also enhanced the phosphorylation of ERK1 with a time-dependent manner. Together with these findings, it is concluded that IgA AECA derived from acute stage of HSP may bind to endothelial and enhance endothelial cells to produce IL-8 via MEK/REK signalling pathway.
最近，研究发现患有活动性过敏性紫癜（HSP）的儿童血清可增强人脐静脉内皮细胞（HUVEC）的白细胞介素（IL）-8生成。为进一步确定HSP急性期血清中可能具有增强内皮细胞IL-8生成能力的因子，招募了10例急性期HSP患儿和10名健康对照。采用基于细胞的ELISA法检测IgA抗内皮细胞抗体（AECA）。使用经或未经抗人IgA抗体预处理的活性血清、对照血清以及从血清中提取的免疫球蛋白A（IgA）刺激HUVEC。评估这些因子增强内皮细胞IL-8生成的能力。此外，还通过不同抑制剂检测信号通路，并通过免疫印迹法进行验证。急性期HPS患者血清中IgA AECA水平显著高于对照组（P<0.001）。活性血清可增强内皮细胞IL-8生成（与对照血清相比，P = 0.004），用固定化抗人IgA抗体预处理后，这些血清的这种能力大多被消除。HSP急性期来源的IgA刺激内皮细胞后，其上清液IL-8水平在统计学上高于对照组（P<0.001）。ERK磷酸化抑制剂PD98059可显著降低IgA AECA刺激的内皮细胞IL-8生成。IgA AECA还以时间依赖性方式增强ERK1的磷酸化。综合这些发现，得出结论：HSP急性期来源的IgA AECA可能与内皮细胞结合，并通过MEK/REK信号通路增强内皮细胞产生IL-8。
