First Author | Miller AL | Year | 2003 |
Journal | J Immunol | Volume | 170 |
Issue | 6 | Pages | 3348-56 |
PubMed ID | 12626595 | Mgi Jnum | J:82293 |
Mgi Id | MGI:2652006 | Doi | 10.4049/jimmunol.170.6.3348 |
Citation | Miller AL, et al. (2003) CXCR2 regulates respiratory syncytial virus-induced airway hyperreactivity and mucus overproduction. J Immunol 170(6):3348-56 |
abstractText | Severe inflammation and mucus overproduction are partially responsible for respiratory syncytial virus (RSV)-induced disease in infants. Using a murine model, we characterized the virally induced chemokine receptors responsible for mediating the pathophysiological response to RSV infection, we found that CXCR2 mRNA was induced at 4 days after RSV infection. Immunohistochemical staining demonstrated that CXCR2 protein was expressed on alveolar macrophages. Immunoneutralization of CXCR2 resulted in decreased airway hyperreactivity relative to the RSV-infected controls. In addition, there was decreased mucus in the bronchoalveolar lavage fluid, decreased periodic-acid Schiff staining, and significantly less mucus-associated gob-5 mRNA and protein in anti-CXCR2-treated mice. The effects of anti-CXCR2 treatment were not a result of differences in viral clearance or neutrophil influx, as these parameters were comparable in both groups of animals. To confirm our immunoneutralization studies, we performed experiments in CXCR2(-/-) mice. Results in CXCR2(-/-) mice recapitulated results from our immunoneutralization studies. However, CXCR2(-/-) mice also showed a statistically significant decrease in muc5ac, relative to RSV-infected wild-type animals. Thus, CXCR2 may be a relevant target in the pathogenesis of RSV bronchiolitis, since it contributes to mucus production and airway hyperreactivity in our model of RSV infection. |