Molecular Pathogenesis of Eye Infection Research Center, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
J Interferon Cytokine Res. 2009 Oct;29(10):657-66. doi: 10.1089/jir.2009.0006.
Epidemic keratoconjunctivitis (EKC), caused by human adenovirus (HAdV), is one of the most common ocular infections and results in corneal inflammation and subepithelial infiltrates. Adenoviral keratitis causes significant morbidity to the patients, and is characterized by infiltration of leukocytes in the corneal stroma, and expression of chemokines. The exact role of these chemokines in adenoviral infection has not been studied due to lack of animal models. Here, we have characterized the role of chemokine CXCL1/KC and receptor CXCR2 in adenoviral keratitis using a novel mouse model. Analysis of chemokine expression, leukocyte infiltration, and development of keratitis was performed by ELISA, flow cytometry, and histopathology, respectively. Deficiency of CXCL1 and CXCR2 resulted in delayed infiltration of neutrophils, but not inflammatory monocytes in HAdV-37 corneal infection. CXCL1(-/-) mice showed decreased expression of CXCL2/MIP-2, but not CCL2/MCP-1. CXCR2(-/-) mice showed increased expression of CXCL1 and CXCL2, but not CCL2. Both CXCL1(-/-) and CXCR2(-/-) mice demonstrated keratitis similar to wild-type mice. In conclusion, both CXCL1 and CXCR2 play an important role in chemokine expression and neutrophil infiltration following adenoviral corneal infection, but have a redundant role in the development of keratitis.
流行性角膜结膜炎（EKC）由人类腺病毒（HAdV）引起，是最常见的眼部感染之一，可导致角膜炎症和上皮下浸润。腺病毒性角膜炎会导致患者出现明显的发病率，其特征是角膜基质中有白细胞浸润和趋化因子表达。由于缺乏动物模型，这些趋化因子在腺病毒感染中的确切作用尚未得到研究。在这里，我们使用一种新型小鼠模型来描述趋化因子 CXCL1/KC 和受体 CXCR2 在腺病毒性角膜炎中的作用。通过 ELISA、流式细胞术和组织病理学分别分析趋化因子表达、白细胞浸润和角膜炎的发展情况。CXCL1 和 CXCR2 缺陷导致 HAdV-37 角膜感染中中性粒细胞浸润延迟，但不影响炎症性单核细胞。CXCL1(-/-) 小鼠表现出 CXCL2/MIP-2 表达减少，但 CCL2/MCP-1 表达不受影响。CXCR2(-/-) 小鼠表现出 CXCL1 和 CXCL2 表达增加，但 CCL2 不受影响。CXCL1(-/-) 和 CXCR2(-/-) 小鼠的角膜炎均与野生型小鼠相似。总之，CXCL1 和 CXCR2 在腺病毒角膜感染后趋化因子表达和中性粒细胞浸润中均发挥重要作用，但在角膜炎的发展中具有冗余作用。
