CXCR2 is required for neutrophilic airway inflammation and hyperresponsiveness in a mouse model of human rhinovirus infection.
CXCR2 is required for neutrophilic airway inflammation and hyperresponsiveness in a mouse model of human rhinovirus infection.
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DOI：
10.4049/jimmunol.0900298
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发表时间：
2009-11-15
期刊：
影响因子：
--
通讯作者：
Hershenson MB
中科院分区：
文献类型：
--
作者：
Nagarkar DR;Wang Q;Shim J;Zhao Y;Tsai WC;Lukacs NW;Sajjan U;Hershenson MB
人鼻病毒（RV）感染是大多数病毒诱导的哮喘急性发作的原因。使用人RV感染的小鼠模型，我们试图确定CXCR 2（ELR阳性CXC趋化因子的受体）对RV诱导的气道嗜肺性和高反应性的需求。野生型和CXCR 2 −/−小鼠鼻内接种RV 1B或假HeLa细胞上清液。在RV 1B感染后，与野生型小鼠相比，CXCR 2 −/−小鼠表现出气道和肺中性粒细胞以及胆碱能反应性降低。在用Ly 6 G的中和抗体（一种嗜中性粒细胞消耗抗体）处理的小鼠中获得了类似的结果。与RV处理的野生型小鼠相比，RV感染的CXCR 2 −/−小鼠的肺显示肿瘤坏死因子（TNF）-α、MIP-2/CXCL 2和KC/CXCL 1的产生显著减少，MUC 5 B的表达也较低。使用TNF受体（TNFR）-1 −/−小鼠检测RV 1B诱导的气道反应对TNF-α的需求。TNFR 1-/-动物显示气道对RV 1B的反应性降低，即使在气道中加入外源性MIP-2。我们的结论是CXCR 2是RV诱导的嗜中性粒细胞气道炎症所必需的，而中性粒细胞TNF-α的释放是气道高反应性所必需的。
Human rhinovirus (RV) infection is responsible for the majority of virus-induced asthma exacerbations. Using a mouse model of human RV infection, we sought to determine the requirement of CXCR2, the receptor for ELR-positive CXC chemokines, for RV-induced airway neutrophilia and hyperresponsiveness. Wild-type and CXCR2 −/− mice were inoculated intranasally with RV1B or sham HeLa cell supernatant. Following RV1B infection, CXCR2 −/− mice showed reduced airway and lung neutrophils and cholinergic responsiveness compared to wild-type mice. Similar results were obtained in mice treated with neutralizing antibody to Ly6G, a neutrophil-depleting antibody. Lungs from RV-infected, CXCR2 −/− mice showed significantly reduced production of tumor necrosis factor (TNF)-α, MIP-2/CXCL2 and KC/CXCL1, and lower expression of MUC5B, compared to RV-treated wild-type mice. The requirement of TNF-α for RV1B-induced airways responses was tested using TNF receptor (TNFR)-1 −/− mice. TNFR1 −/− animals displayed reduced airways responsiveness to RV1B, even when exogenous MIP-2 was added to the airways. We conclude that CXCR2 is required for RV-induced neutrophilic airway inflammation, and that neutrophil TNF-α release is required for airways hyperresponsiveness.
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