Research on the innate immune system of the cornea

为了阐明角膜细胞在角膜先天免疫系统中的作用，我们揭示了以下事实：1)培养的人角膜成纤维细胞表达toll样受体(TLR)-4和分化簇（CD） 14，它们是LPS受体的组成部分。这些细胞还表达MD-2蛋白，这是LPS受体在细胞膜上合理分布所必需的。2)大肠杆菌、绿绿p.a rubginosa和S Minnesota来源的LPS增强了培养的人角膜成纤维细胞IL-8、MCP-1和ICAM-1的表达。这种效应是时间和剂量依赖的。LPS对这些蛋白表达的影响是E.coli> s.m nminnesota >> p.a ulugnosa3)人泪液中确实含有LBP和sCD14。这些lps相关蛋白的浓度分别约为1微克/毫升和400纳克/毫升。这些脂多糖相关蛋白在泪液中的浓度低于在相同设置下测量的血清中的浓度。泪液中这些脂多糖相关蛋白的浓度与血清之间没有明显的关系。4)添加LBP或sCD14诱导培养的人角膜成纤维细胞IL-8释放和ICAM-1表达呈剂量依赖性增加。血清中脂多糖相关蛋白的刺激作用比泪液中脂多糖的刺激作用更明显。将脂多糖注射到兔角膜基质中可引起角膜溃疡和角膜混浊。这些角膜损伤是短暂的，角膜会自行愈合，留下角膜瘢痕。组织学上，中性粒细胞浸润到角膜基质中。我们的研究表明，角膜细胞，特别是角膜成纤维细胞，在外眼的先天免疫系统中起作用。这些细胞感知LPS的存在，这是革兰氏阴性细菌细胞壁的常见结构，并表达中性粒细胞活化和趋化因子如ICAM-1和il - 8lps相关蛋白如LBP或sCD14，增强角膜细胞对LPS的感知

In order to clarify the roles of corneal cells in innate immune system of the cornea, we revealed the following facts1) Cultured human corneal fibroblasts express toll-like receptor (TLR)-4 and cluster of differentiation (CD) 14, which are the components of LPS receptors. These cells also express MD-2 protein, which is necessary for the proper distribution of LPS receptors on the cell membrane2) LPS derived from E Coli, P.aerubginosa and S Minnesota enhanced the expression of IL-8, MCP-1 and ICAM-1 by cultured human corneal fibroblast. This effect was time and dose-dependent. The effect of LPS on the expression on these proteins are E.coli> S.Minnesota>> P.aeruglnosa3) Human tear fluids did contain LBP and sCD14. The concentrations of these LPS-related proteins were about 1 micro gram 1 ml and 400 nano gram /ml, respectively. The concentrations of these LPS-related proteins were lower in the tear fluids than that in the serum measured with a same settings. There were no relationships b … More etween the concentration of these LPS-related proteins in the tear fluids and the serum4) Addition of LBP or sCD14 induced a dose dependent increase of IL-8 release and ICAM-1 expression by cultured human corneal fibroblasts. The stimulatory effect of these LPS-related proteins axe more pronounced at a concentration of the serum than that of the tear fluids5) Injection of LPS into a rabbit corneal stroma induced a corneal ulcer and corneal opacity. These corneal lesions are transient the cornea is healed spontaneously leaving corneal scarring. Histologically, infiltration of neutrophils is observed in to the corneal stromaOur study shows that the cells of the cornea, especially the corneal fibroblasts, play a role in the innate immune system of the outer eye. These cells perceive the presence of LPS, which is a common structure of Gram negative bacterial cell walls, and express neutrophils activation and chemotactic factors such as ICAM-1 and IL-8LPS-related proteins such as LBP or sCD14 enhance the perception of LPS by corneal cells Less