Roles of Lung Epithelium in Neutrophil Recruitment During Pneumococcal Pneumonia

ArticleinAmerican Journal of Respiratory Cell and Molecular Biology 50(2) · September 2013with17 Reads
Impact Factor: 3.99 · DOI: 10.1165/rcmb.2013-0114OC · Source: PubMed

    Abstract

    Epithelial cells line the respiratory tract and interface with the external world. Epithelial cells contribute in some fashion to pulmonary inflammation, but specific epithelial roles have proven difficult to define. To discover unique epithelial activities that influence immunity during infection, we generated mice with NF-κB RelA mutated throughout all epithelial cells of the lung, and we coupled this approach with epithelial cell isolation from infected and uninfected lungs for cell-specific analyses of gene induction. The RelA mutant mice appeared normal basally, but in response to pneumococcus in the lungs they were unable to rapidly recruit neutrophils to the air spaces. Epithelial cells expressed multiple neutrophil-stimulating cytokines during pneumonia, all of which depended on RelA. Cytokine expression by non-epithelial cells was unaltered by the epithelial mutation of RelA. Epithelial cells were the predominant sources of CXCL5 and GM-CSF, while non-epithelial cells were major sources for other neutrophil-activating cytokines. Epithelial RelA mutation decreased whole lung levels of CXCL5 and GM-CSF during pneumococcal pneumonia, while lung levels of other neutrophil-recruiting factors were unaffected. Defective neutrophil recruitment in epithelial mutant mice could be rescued by administration of CXCL5 or GM-CSF. These results reveal a specialized immune function for the pulmonary epithelium, the induction of CXCL5 and GM-CSF to accelerate neutrophil recruitment in the infected lung.