Chen A, Chen W P, Sheu L F, Lin C Y
Department of Medical Research, Veterans General Hospital-Taipei, Taiwan, Republic of China.
J Pathol. 1994 Jun;173(2):119-26. doi: 10.1002/path.1711730208.
IgA immune complex (IC) plays a crucial role in the pathogenesis of IgA nephropathy (IgAN). As IgA-IC is not itself cytotoxic, other mediators may be involved in the pathogenesis. In order to elucidate the mechanisms by which IgA-IC mediates renal injury in IgAN, the ability of IgA-IC to 'activate' cultured human mesangial cells (HMC) was studied. HMC were incubated with nephritogenic IgA-IC, containing a MOPC-315 plasmacytoma-derived IgA anti-dinitrophenyl (DNP) and DNP-conjugated bovine serum albumin. The cells showed morphological changes, an accelerated rate of proliferation, and increased production of interleukin-1 (IL-1), interleukin-6 (IL-6), platelet activating factor (PAF) and generation of superoxide anion. The enhancement of IL-1 and IL-6 mRNA expression in HMC incubated with IgA-IC was identified by dot blot analysis. Northern blot hybridization also demonstrated an augmented IL-6 mRNA expression in HMC treated with IgA-IC. These results suggest that nephritogenic IgA-IC may amplify the proliferation of HMC and the production of immune/chemical mediators and superoxide anion thereby resulting in the renal lesions of IgAN.
IgA免疫复合物（IC）在IgA肾病（IgAN）的发病机制中起关键作用。由于IgA-IC本身没有细胞毒性，其他介质可能参与了发病过程。为了阐明IgA-IC介导IgAN肾损伤的机制，研究了IgA-IC “激活” 培养的人系膜细胞（HMC）的能力。将HMC与致肾炎性IgA-IC一起孵育，该IgA-IC含有源自MOPC-315浆细胞瘤的IgA抗二硝基苯基（DNP）和DNP偶联的牛血清白蛋白。细胞出现形态变化、增殖速率加快，白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、血小板活化因子（PAF）的产生增加以及超氧阴离子的生成。通过斑点印迹分析确定了与IgA-IC孵育的HMC中IL-1和IL-6 mRNA表达的增强。Northern印迹杂交也证明了用IgA-IC处理的HMC中IL-6 mRNA表达增加。这些结果表明，致肾炎性IgA-IC可能会放大HMC的增殖以及免疫/化学介质和超氧阴离子的产生，从而导致IgAN的肾损伤。
