Suzuma K, Mandai M, Kogishi J, Tojo S J, Honda Y, Yoshimura N
Department of Opthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Japan.
Invest Ophthalmol Vis Sci. 1997 Jul;38(8):1610-8.
P-selectin is one of the early-reactive adhesion molecules that play a part in the rolling phase of leukocytes in cellular infiltration. The study objective was to determine whether P-selectin is involved in the development of endotoxin-induced uveitis (EIU).
Endotoxin-induced uveitis was initiated in male Lewis rats by injecting 200 micrograms lipopolysaccharide (LPS) into the foot pad. Expression of P-selectin in the iris-ciliary body was studied by immunohistochemistry using wholemounts and paraffin embedded sections of iris-ciliary body prepared at various time intervals. A monoclonal antibody (mAb) against P-selectin and a ligand for P-selectin, sialyl Lewis X oligosaccharide (SLeX-OS), was intravenously injected to evaluate the effects of selectin inhibition. The effect of treatment was evaluated by the number of infiltrated cells and protein concentration in the aqueous humor at 24 hours after LPS treatment.
P-selectin immunoreactivities were observed in the vessels of the iris in whole iris-ciliary body mounts and on the surface of the microvascular endothelium in paraffin-embedded sections. Activity was most prominent at 15 minutes and at 5 to 7 hours after LPS treatment and was moderate from 1 to 4 hours after treatment. The selective inhibition of P-selectin significantly blocked the cellular infiltration into aqueous humor, but this infiltration was even more effectively inhibited by SLeX-OS. Protein concentration in the aqueous humor was not inhibited by selectin as much as was cellular infiltration.
In the early phase of EIU, P-selectin may be expressed on the vascular endothelium in the iris in a biphasic pattern that modulates the rolling phase of leukocytes. The expression of this molecule may be essential for succeeding processes of cellular infiltration and may determine the subsequent states of ocular inflammation.
P-选择素是早期反应性黏附分子之一，在细胞浸润过程中白细胞的滚动阶段发挥作用。本研究目的是确定P-选择素是否参与内毒素诱导的葡萄膜炎（EIU）的发生发展。
通过向雄性Lewis大鼠足垫注射200微克脂多糖（LPS）引发内毒素诱导的葡萄膜炎。使用虹膜睫状体整装片和不同时间间隔制备的虹膜睫状体石蜡包埋切片，通过免疫组织化学研究虹膜睫状体中P-选择素的表达。静脉注射抗P-选择素单克隆抗体（mAb）和P-选择素配体唾液酸化路易斯X寡糖（SLeX-OS），以评估选择素抑制的效果。在LPS处理后24小时，通过房水中浸润细胞数量和蛋白浓度评估治疗效果。
在整个虹膜睫状体整装片中虹膜血管以及石蜡包埋切片的微血管内皮表面观察到P-选择素免疫反应性。LPS处理后15分钟和5至7小时活性最为显著，处理后1至4小时活性中等。P-选择素的选择性抑制显著阻断了细胞向房水的浸润，但SLeX-OS对这种浸润的抑制作用更有效。房水中的蛋白浓度受选择素的抑制程度不如细胞浸润。
在EIU的早期阶段，P-选择素可能以双相模式在虹膜血管内皮上表达，调节白细胞的滚动阶段。该分子的表达可能对细胞浸润的后续过程至关重要，并可能决定眼部炎症的后续状态。
