Sonoda Koh-Hei, Sasa Yukio, Qiao Hong, Tsutsumi Chikako, Hisatomi Toshio, Komiyama Sohtaro, Kubota Toshiaki, Sakamoto Taiji, Kawano Yoh-Ichi, Ishibashi Tatsuro
Department of Ophthalmology, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
J Immunol. 2003 Sep 1;171(5):2652-9. doi: 10.4049/jimmunol.171.5.2652.
Murine experimental autoimmune uveitis (EAU) is a model of human uveitis. Ocular-infiltrating macrophages play a crucial role in the generation of tissue damage in EAU. In fact, several chemokines are actually produced in the inflamed eye. The aim of this study was to elucidate the role of ocular macrophage-derived chemokines in EAU. C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein peptide 1-20, and the EAU severity was scored at multiple time points based on microscopic fundus observations (retinal vascular dilatation and exudates) and histological examinations. The peak inflammatory response was observed 1 wk (day 16) after the beginning of macrophage infiltration to the eye (day 9). Ocular-infiltrating cells were enriched or depleted of macrophages by magnetic beads and analyzed by real-time RT-PCR for chemokine mRNA production. We found that only the macrophage-enriched cells from the eye produced RANTES, and thus proposed that macrophage-derived RANTES facilitated the ocular inflammations. In contrast to our postulate, neutralization of RANTES by specific Ab in vivo on days 9 and 13 exacerbated EAU. We also found that the ratio of ocular CD4/CD8 T cells was markedly increased after treatment. As a result, RANTES neutralization might exacerbate EAU by modulating the type of T cell subsets recruited to the eye. In conclusion, our data provide insight into the immunoregulatory role of macrophages and RANTES in the pathogenesis of ocular inflammation. Not all macrophage-derived chemokines cause local inflammation, since RANTES produced by ocular macrophages appears to suppress EAU.
小鼠实验性自身免疫性葡萄膜炎（EAU）是人类葡萄膜炎的一种模型。眼内浸润的巨噬细胞在EAU组织损伤的发生中起关键作用。事实上，几种趋化因子确实在炎症眼中产生。本研究的目的是阐明眼巨噬细胞衍生趋化因子在EAU中的作用。用人类光感受器间维生素A结合蛋白肽1 - 20免疫C57BL/6小鼠，并根据眼底显微镜观察（视网膜血管扩张和渗出物）和组织学检查在多个时间点对EAU严重程度进行评分。在巨噬细胞开始浸润到眼睛（第9天）后1周（第16天）观察到炎症反应高峰。通过磁珠富集或去除眼内浸润细胞中的巨噬细胞，并通过实时RT-PCR分析趋化因子mRNA的产生。我们发现只有来自眼睛的富含巨噬细胞的细胞产生RANTES，因此提出巨噬细胞衍生的RANTES促进了眼部炎症。与我们的假设相反，在第9天和第13天在体内用特异性抗体中和RANTES会加重EAU。我们还发现治疗后眼内CD4/CD8 T细胞的比例显著增加。因此，RANTES中和可能通过调节募集到眼睛的T细胞亚群类型而加重EAU。总之，我们的数据为巨噬细胞和RANTES在眼部炎症发病机制中的免疫调节作用提供了见解。并非所有巨噬细胞衍生的趋化因子都会引起局部炎症，因为眼巨噬细胞产生的RANTES似乎会抑制EAU。
