Georgakopoulos C D, Exarchou A M, Gartaganis S P, Kolonitsiou F, Anastassiou E D, Dimitracopoulos G, Hjerpe A, Theocharis A D, Karamanos N K
Department of Ophthalmology, School of Medicine, University of Patras, Greece, and Department of Laboratory Medicine, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
Curr Eye Res. 2006 Feb;31(2):137-46. doi: 10.1080/02713680500516540.
Staphylococcus epidermidis is a leading cause of bacterial keratitis associated with corneal damage. Corneal integrity is closely associated with matrix macromolecules, such as proteoglycans (PGs) and collagen. The aim of this study was to examine whether active immunization (AI) using a major immunogenic polysaccharide determinant of slime (20-kDa PS) as antigen, and passive immunization (PI) after administration of specific antibodies toward 20-kDa PS affect the distribution of PGs as well as corneal lesions in an experimental model of slime-producing S. epidermidis keratitis.
For AI, seven rabbits were immunized with 20-kDa PS, whereas for PI, seven rabbits received specific antibodies against 20-kDa PS. Lesions were graded clinically for a 21-day period. Levels of 20-kDa PS antibodies in serum and aqueous humor in both immunization groups were determined by ELISA. The distribution of certain extracellular matrix PGs during corneal healing was analyzed immunohistochemically.
Levels of specific anti-20-kDa PS antibodies in serum and aqueous humor obtained after either AI or PI were significantly higher as compared with those in the respective nonimmunized control groups (p<0.001). Clinical grading showed that both AI and PI rabbits had a significantly less corneal damage as compared with infected nontreated rabbits. Immunohistochemical analyses for PGs exhibited significant differences to the wounded regions as compared with noninfected corneal tissue. Accumulation of keratan sulfate PGs and decorin was observed in the corneal stroma of infected rabbits and of heparan sulfate PGs around the new-formed vessels. This phenomenon was significantly reduced in immunized animals in accordance with macroscopically decreased corneal damage observed in these animals.
Results of this study suggest a key role of 20-kDa PS and its antibodies as prophylactic and therapeutic agents in keratitis caused by slime-producing S. epidermidis.
表皮葡萄球菌是与角膜损伤相关的细菌性角膜炎的主要病因。角膜完整性与基质大分子密切相关，如蛋白聚糖（PGs）和胶原蛋白。本研究的目的是在产黏液表皮葡萄球菌角膜炎的实验模型中，研究以黏液主要免疫原性多糖决定簇（20-kDa PS）作为抗原进行主动免疫（AI），以及给予针对20-kDa PS的特异性抗体后进行被动免疫（PI），是否会影响PGs的分布以及角膜病变。
对于主动免疫，7只兔子用20-kDa PS免疫，而对于被动免疫，7只兔子接受针对20-kDa PS的特异性抗体。在21天内对病变进行临床分级。通过酶联免疫吸附测定法（ELISA）测定两个免疫组血清和房水中20-kDa PS抗体的水平。免疫组织化学分析角膜愈合过程中某些细胞外基质PGs的分布。
与各自未免疫的对照组相比，主动免疫或被动免疫后获得的血清和房水中特异性抗20-kDa PS抗体水平显著更高（p<0.001）。临床分级显示，与未治疗的感染兔子相比，主动免疫和被动免疫的兔子角膜损伤明显更少。PGs的免疫组织化学分析显示，与未感染的角膜组织相比，受伤区域存在显著差异。在感染兔子的角膜基质中观察到硫酸角质素PGs和核心蛋白聚糖的积累，以及新生血管周围硫酸乙酰肝素PGs的积累。在免疫动物中，这种现象显著减少，与这些动物中观察到的宏观角膜损伤减少一致。
本研究结果表明20-kDa PS及其抗体在产黏液表皮葡萄球菌引起的角膜炎中作为预防和治疗剂具有关键作用。
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