Chemokine CXCL1/KC and its Receptor CXCR2 Are Responsible for Neutrophil Chemotaxis in Adenoviral Keratitis
Chemokine CXCL1/KC and its Receptor CXCR2 Are Responsible for Neutrophil Chemotaxis in Adenoviral Keratitis
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DOI：
10.1089/jir.2009.0006
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发表时间：
2009-10-01
影响因子：
2.3
通讯作者：
Chodosh, James
中科院分区：
文献类型：
--
作者：
Chintakuntlawar, Ashish V.;Chodosh, James
流行性角膜结膜炎（EKC）是由人腺病毒（HAdV）引起的一种常见的眼部感染，可导致角膜炎症和上皮下浸润。腺病毒性角膜炎引起患者的显著发病率，并且其特征在于角膜基质中的白细胞浸润和趋化因子的表达。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研究。在这里，我们的特点是趋化因子CXCL 1/KC和受体CXCR 2在腺病毒性角膜炎使用一种新的小鼠模型的作用。分别通过ELISA、流式细胞术和组织病理学分析趋化因子表达、白细胞浸润和角膜炎的发展。在HAdV-37角膜感染中，CXCL 1和CXCR 2的缺乏导致中性粒细胞的延迟浸润，但不导致炎性单核细胞的浸润。CXCL 1（-/-）小鼠显示CXCL 2/MIP-2表达降低，但不显示CCL 2/MCP-1表达降低。CXCR 2（-/-）小鼠显示CXCL 1和CXCL 2的表达增加，但不显示CCL 2。CXCL 1（-/-）和CXCR 2（-/-）小鼠均表现出与野生型小鼠相似的角膜炎。总之，CXCL 1和CXCR 2在腺病毒角膜感染后趋化因子表达和中性粒细胞浸润中发挥重要作用，但在角膜炎的发展中具有多余的作用。
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.