Key Molecules involved in the Early Phase of Anterior Uveitis

内毒素诱导性葡萄膜炎(EIU)是由注射脂多糖(LPS)引起的急性眼部炎症的动物模型。选择素区域参与白细胞滚动的一组分子，这是细胞渗透的初始步骤。其中，P-选择素储存在血管内皮细胞体中，并在刺激时转移到血管表面，而E-选择素则在基因转录水平上进行调控。在EIU中，我们发现P-选择素在内毒素处理后15min出现在虹膜睫状体血管内皮细胞表面，在注射后3-5h再次表达，E-选择素在内毒素处理后7-24小时出现。抗P-选择素和E-选择素的中和抗体均可减少EIU中的细胞浸润，但在脂多糖处理后6小时给予抗P-选择素抗体并不能显著抑制细胞的渗透，而抗E-选择素抗体…在内毒素治疗后的任何时间给予更多，可显著减少此后的细胞渗透。半定量聚合酶链式反应显示，E-选择素基因在内毒素治疗后6h在虹膜睫状体和视网膜中的表达均达到高峰，并在最大葡萄膜炎时恢复到基础水平。同时注射抗P-选择素和E-选择素抗体几乎消除了细胞的浸润。提示P-选择素参与了细胞浸润的启动，而E-选择素有助于保持细胞的浸润，抑制P-选择素可能有助于预防炎症，抑制E-选择素有助于炎症的早期消退。接下来，我们关注前葡萄膜炎合并大量细胞浸润的事实，男性比女性更常见，我们正在研究雌激素在EIU中抗细胞渗透的作用。在虹膜睫状体血管内皮细胞上发现了雌激素受体样免疫反应，细胞浸润的程度按去卵巢的雌性和雌性大鼠的顺序排列。腹腔注射雌二醇可显著减少细胞浸润和E-选择素基因的表达，提示雌激素通过调节选择素的表达来保护细胞不受细胞浸润的侵袭。较少

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