CXCR2 Is Required for Neutrophilic Airway Inflammation and Hyperresponsiveness in a Mouse Model of Human Rhinovirus Infection

被引：79

作者：

Nagarkar, Deepti R. ^{[1
]}

Wang, Qiong ^{[1
]}

Shim, Jee ^{[2
]}

Zhao, Ying ^{[2
]}

Tsai, Wan C. ^{[2
]}

Lukacs, Nicholas W. ^{[3
]}

Sajjan, Uma ^{[2
]}

Hershenson, Marc B. ^{[1
,2
]}

机构：

[1] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 183卷 / 10期

基金：

美国国家卫生研究院;

关键词：

ASTHMATIC SUBJECTS; EPITHELIAL-CELLS; BONE-MARROW; RECEPTOR; EXPRESSION; INTERLEUKIN-8; INDUCTION; COLDS; CYTOKINE; MEMBERS;

D O I：

10.4049/jimmunol.0900298

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 with wild-type mice. Similar results were obtained in mice treated with neutralizing Ab to Ly6G, a neutrophil-depleting Ab. Lungs from RV-infected, CXCR2(-/-) mice showed significantly reduced production of TNF-alpha, MIP-2/CXCL2, and KC/CXCL1 and lower expression of MUC5B compared with RV-treated wild-type mice. The requirement of TNF-alpha for RV1B-induced airway responses was tested using TNFR1(-/-) mice. TNFR1(-/-) animals displayed reduced airway 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-alpha release is required for airway hyperresponsiveness. The Journal of Immunology, 2009, 183: 6698-6707.

引用

页码：6698 / 6707

页数：10

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