Institute of Animal Physiology, Department for Veterinary Sciences, Ludwig-Maximilians University, Veterinärstr. 13, D-80539 Munich, Germany.
Immunobiology. 2010 Dec;215(12):949-55. doi: 10.1016/j.imbio.2010.02.003. Epub 2010 Mar 1.
Equine recurrent uveitis serves as a spontaneous model for human autoimmune uveitis. Unpredictable relapses and ongoing inflammation in the eyes of diseased horses as well as in humans lead to destruction of the retina and finally result in blindness. However, the molecular mechanisms leading to inflammation and retinal degeneration are not well understood. An initial screening for differentially regulated proteins in sera of uveitic cases compared to healthy controls revealed an increase of the alternative pathway complement component factor B in ERU cases. To determine the activation status of the complement system, sera were subsequently examined for complement split products. We could demonstrate a significant higher concentration of the activation products B/Ba, B/Bb, Bb neoantigen, iC3b and C3d in uveitic condition compared to healthy controls, whereas for C5b-9 no differences were detected. Additionally, we investigated complement activation directly in the retina by immunohistochemistry, since it is the main target organ of this autoimmune disease. Interestingly, infiltrating cells co-expressed activated factor Bb neoantigen, complement split product C3d as well as CD68, a macrophage marker. In this study, we could demonstrate activation of the complement system both systemically as well as in the eye, the target organ of spontaneous recurrent uveitis. Based on these novel findings, we postulate a novel role for macrophages in connection with complement synthesis at the site of inflammation.
马的复发性葡萄膜炎是人类自身免疫性葡萄膜炎的自发模型。患病马匹和人类的眼睛中不可预测的复发和持续炎症会导致视网膜破坏，最终导致失明。然而，导致炎症和视网膜变性的分子机制尚不清楚。对葡萄膜炎病例与健康对照血清中差异调节蛋白的初步筛选显示，ERU 病例中替代途径补体成分因子 B 增加。为了确定补体系统的激活状态，随后检查了血清中的补体裂解产物。与健康对照组相比，我们可以证明在葡萄膜炎状态下，激活产物 B/Ba、B/Bb、Bb 新抗原、iC3b 和 C3d 的浓度显著升高，而 C5b-9 则没有差异。此外，我们通过免疫组织化学直接在视网膜中研究补体激活，因为它是这种自身免疫性疾病的主要靶器官。有趣的是，浸润细胞共同表达激活的因子 Bb 新抗原、补体裂解产物 C3d 以及巨噬细胞标志物 CD68。在这项研究中，我们可以证明补体系统在全身和眼睛（自发复发性葡萄膜炎的靶器官）中的激活。基于这些新发现，我们推测巨噬细胞在炎症部位与补体合成有关的新作用。
