RGD Reference Report - CXCR2 is required for neutrophilic airway inflammation and hyperresponsiveness in a mouse model of human rhinovirus infection. - Rat Genome Database

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CXCR2 is required for neutrophilic airway inflammation and hyperresponsiveness in a mouse model of human rhinovirus infection.

Authors: Nagarkar, DR  Wang, Q  Shim, J  Zhao, Y  Tsai, WC  Lukacs, NW  Sajjan, U  Hershenson, MB 
Citation: Nagarkar DR, etal., J Immunol. 2009 Nov 15;183(10):6698-707. Epub 2009 Oct 28.
RGD ID: 5131210
Pubmed: (View Article at PubMed) PMID:19864593
DOI: Full-text: DOI:10.4049/jimmunol.0900298

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.

Annotation

Disease Annotations    
common cold  (IMP,ISO)
Enterovirus Infections  (IMP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Cxcr2  (C-X-C motif chemokine receptor 2)
Tnfrsf1a  (TNF receptor superfamily member 1A)

Genes (Mus musculus)
Cxcr2  (chemokine (C-X-C motif) receptor 2)
Tnfrsf1a  (tumor necrosis factor receptor superfamily, member 1a)

Genes (Homo sapiens)
CXCR2  (C-X-C motif chemokine receptor 2)
TNFRSF1A  (TNF receptor superfamily member 1A)


Additional Information