Key Molecules involved in the Early Phase of Anterior Uveitis

内毒素性葡萄膜炎（EIU）是一种由脂多糖（LPS）引起的急性眼部炎症的动物模型。选择素是一组参与白细胞滚动的分子，这是细胞浸润的第一步。其中p -选择素储存在血管内皮细胞体中，受刺激后易位到表面，而e -选择素受基因转录水平调控。在EIU中，我们发现p -选择素在LPS处理15分钟后出现在虹膜-睫状体血管内皮表面，在LPS注射后3-5小时出现第二次表达，e -选择素在LPS处理后7-24小时出现。P-和e -选择素的中和抗体均减少了EIU的细胞浸润，但在LPS处理后6小时给予抗P-选择素抗体对EIU的细胞浸润没有显著抑制作用，而在LPS处理后任何时间给予抗e -选择素抗体则显著减少了EIU的细胞浸润。半定量PCR结果显示，在LPS处理后6小时，E-selectin基因在虹膜睫状体和视网膜中的表达达到峰值，在葡萄膜炎最严重的时候回到基础水平。同时注射抗p -和e -选择素抗体几乎可以消除细胞浸润。这表明p -选择素参与细胞浸润的开始，而e -选择素有助于保持细胞浸润；抑制前者可能有助于预防炎症，后者可能有助于炎症的早期消退。接下来我们关注的事实是，与大量细胞浸润相关的前葡萄膜炎在男性中比在女性中更常见，我们正在研究雌激素在EIU中对抗细胞浸润的作用。虹膜-睫状体血管内皮有雌激素受体样免疫反应，细胞浸润程度与雄性>去卵巢雌性>大鼠顺序相同。腹腔注射雌二醇可显著降低细胞浸润和e -选择素基因表达，提示雌激素通过调节选择素的表达来抑制细胞浸润。少

Endotoxin-induced uveitis (EIU) is an animal model of acute ocular inflammation caused by the injection of lipopolysaccharide (LPS). Selectins area group of molecules involved in rolling of leukocytes, the initial step of cellular infiltration. Among them, P-selectin is stored in the vascular endothelial cell body and translocated to the surface upon stimulation, whereas E-selectin is regulated at the transcriptional level of the gene. In EIU, we found that P-selectin appeared immunohistochemically on the endothelial surface of the vessels of iris-ciliary body after 15 minutes of LPS treatment, followed by its second expression at 3-5 hours after LPS injection, and that E-selectin appeared 7-24 hours after LPS treatment. Each of the neutralizing antibodies against P- and E-selectin similarly reduced the cellular infiltration in EIU, but anti P-selectin antibody given at 6 hours after LPS treatment did not significantly inhibit the cellular infiltration whereas anti E-selectin antibody … More given at any time after LPS treatment significantly reduced cellular infiltration thereafter. Semi-quantitative PCR revealed that E-selectin gene expression reached a peak at 6 hours after LPS treatment both in the iris-ciliary body and retina, and it returned to the basal level at the time of maximum uveitis. Simultaneous injection of anti P-and E-selectin antibodies almost abrogated cellular infiltration. These suggested that P-selectin is involved in the initiation of cellular infiltration whereas E-selectin contributes to retain cellular infiltration ; the inhibition of the former may contribute to the prevention of inflammation and the latter, to the early resolution of the inflammation. Next we focused on the fact that anterior uveitis associated with massive cellular infiltration is more often observed in men than in women, and we are studying the role of estrogen against cellular infiltration in EIU.Estrogen receptor-like immunoreactivity was found on the vascular endothelium of iris-ciliary body, and the degree of cellular infiltration was in the order of male>ovariectomized female>female rats. Intraperitoneal injection of estradiol significantly reduced cellular infiltration and the E-selectin gene expression, indicating that estrogen protects against cellular infiltration by modulation the selectin expression. Less