Khan Shamila, Cole Nerida, Hume Emma B, Garthwaite Linda, Conibear Timothy C R, Miles David H, Aliwaga Yulina, Krockenberger Mark B, Willcox Mark D P
Intitute for Eye Research, and School of Optometry, University of New South Wales, Sydney, NSW 2052, Australia.
J Leukoc Biol. 2007 Jan;81(1):315-8. doi: 10.1189/jlb.0506344. Epub 2006 Oct 6.
Pseudomonas is one of the leading causes of contact lens-related microbial keratitis. Despite the use of antibiotics, the host inflammatory response continues to cause damage to the cornea, which may lead to blindness. CXCR2-binding chemokines have been implicated in the pathogenesis of Pseudomonas keratitis, and the exact role of this receptor remains to be elucidated. Corneas of CXCR2 knockout and wild-type mice (Cmkar 2-/- and Cmkar 2+/+) were scratched, and 2x10(6) CFU/mL Pseudomonas 6294 or 6206 was added to corneas. Twenty-four hours postinfection, mice were killed, and eyes were harvested for enumeration of bacteria, myeloperoxidase (MPO) levels, and inflammatory mediators. Cmkar 2-/- had 20- to 100-fold more bacteria than Cmkar 2+/+ mice. There were no differences in MPO levels between gene knockout and Cmkar 2+/+ mice. Histology revealed PMN were restricted to the limbal area. Levels of CXCR2 chemokines (keratinocyte-derived chemokine and MIP-2) were elevated significantly in gene knockout mice. A lack of CXCR2 leads to an inability to control bacterial numbers as a result of the inability of PMN to reach the site of infection in the avascular cornea. These results imply that CXCR2 is critical to the extravasation of neutrophils into the avascular cornea.
铜绿假单胞菌是与隐形眼镜相关的微生物性角膜炎的主要病因之一。尽管使用了抗生素，但宿主的炎症反应仍会继续对角膜造成损害，这可能导致失明。CXCR2结合趋化因子与铜绿假单胞菌角膜炎的发病机制有关，而该受体的确切作用仍有待阐明。刮伤CXCR2基因敲除小鼠和野生型小鼠（Cmkar 2-/-和Cmkar 2+/+）的角膜，并向角膜中加入2×10(6) CFU/mL的铜绿假单胞菌6294或6206。感染后24小时，处死小鼠并摘取眼睛，用于细菌计数、髓过氧化物酶（MPO）水平检测及炎症介质分析。与Cmkar 2+/+小鼠相比，Cmkar 2-/-小鼠角膜中的细菌数量多20至100倍。基因敲除小鼠与Cmkar 2+/+小鼠的MPO水平没有差异。组织学检查显示多形核白细胞局限于角膜缘区域。基因敲除小鼠中CXCR2趋化因子（角质形成细胞衍生趋化因子和MIP-2）的水平显著升高。由于多形核白细胞无法到达无血管角膜的感染部位，缺乏CXCR2会导致无法控制细菌数量。这些结果表明，CXCR2对于中性粒细胞渗入无血管角膜至关重要。
