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

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2009 Oct 30

PMID 19864593

Citations 57

Authors

Deepti R Nagarkar

Qiong Wang

Jee Shim

Ying Zhao

Wan C Tsai

Nicholas W Lukacs

Uma Sajjan

Marc B Hershenson

Affiliations

Soon will be listed here.

Abstract

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.

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