Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.
Mol Immunol. 2010 Nov-Dec;48(1-3):231-9. doi: 10.1016/j.molimm.2010.08.006. Epub 2010 Sep 16.
This study was initiated to explore the effect of recombinant rat Crry linked to the Fc portion of rat IgG2a (Crry-Ig) on the induction of experimental autoimmune anterior uveitis (EAAU) and on established disease. EAAU was induced in Lewis rats by immunization with bovine melanin-associated antigen (MAA). MAA sensitized animals received Crry-Ig, rat IgG2a (isotype control) or PBS separately before the onset of EAAU or after the onset of clinical disease. Administration of Crry-Ig suppressed the induction of EAAU while all animals injected with IgG2a or PBS developed the normal course of EAAU. Treatment with Crry-Ig resulted in the suppression of ocular complement activation as well as the functional activity of complement in the peripheral blood. At the peak of EAAU, levels of IFN-γ, IP-10, ICAM-1 and LECAM-1 were significantly reduced within the eyes of Crry-Ig treated Lewis rats. Importantly, administration of Crry-Ig even after the onset of EAAU resulted in a sharp decline in the disease activity and early resolution of EAAU. Collectively, the evidence presented here demonstrate that inhibition of complement by Crry-Ig results in low levels of inflammatory molecules-C3 activation products, MAC, cytokines, chemokines and adhesion molecules in the eye. Down-regulation of these molecules affects the infiltration and recruitment of inflammatory cells to the eye resulting in the inhibition of EAAU.
这项研究旨在探讨与大鼠 IgG2a 的 Fc 部分连接的重组大鼠 Crry（Crry-Ig）对实验性自身免疫前葡萄膜炎（EAAU）诱导和已建立疾病的影响。通过用牛黑色素相关抗原（MAA）免疫Lewis 大鼠诱导 EAAU。MAA 致敏动物在 EAAU 发作前或临床疾病发作后分别接受 Crry-Ig、大鼠 IgG2a（同种型对照）或 PBS 治疗。Crry-Ig 的给药抑制了 EAAU 的诱导，而所有接受 IgG2a 或 PBS 注射的动物均发展为正常的 EAAU 病程。Crry-Ig 的治疗导致眼部补体激活以及外周血中补体的功能活性受到抑制。在 EAAU 的高峰期，Crry-Ig 治疗的 Lewis 大鼠眼内 IFN-γ、IP-10、ICAM-1 和 LECAM-1 的水平显著降低。重要的是，即使在 EAAU 发作后给予 Crry-Ig，也会导致疾病活动急剧下降和 EAAU 的早期缓解。总之，这里提供的证据表明，Crry-Ig 抑制补体导致眼内炎症分子-C3 激活产物、MAC、细胞因子、趋化因子和粘附分子的水平降低。这些分子的下调会影响炎症细胞向眼部的浸润和募集，从而抑制 EAAU。
