Epithelial cell-derived secreted and transmembrane 1a signals to activated neutrophils during pneumococcal pneumonia

Hirofumi Kamata, Kazuko Yamamoto, Gregory A. Wasserman, Mary C. Zabinski, Constance K. Yuen, Wing Yi Lung, Adam C. Gower, Anna C. Belkina, Maria I. Ramirez, Jane C. Deng, Lee J. Quinton, Matthew R. Jones, Joseph P. Mizgerd

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Airway epithelial cell responses are critical to the outcome of lung infection. In this study, we aimed to identify unique contributions of epithelial cells during lung infection. To differentiate genes induced selectively in epithelial cells during pneumonia, we compared genome-wide expression profiles from three sorted cell populations: epithelial cells from uninfected mouse lungs, epithelial cells from mouse lungs with pneumococcal pneumonia, and nonepithelial cells from those same infected lungs. Of 1,166 transcripts that were more abundant in epithelial cells from infected lungs compared with nonepithelial cells from the same lungs or from epithelial cells of uninfected lungs, 32 genes were identified as highly expressed secreted products. Especially strong signals included two related secreted and transmembrane (Sectm) 1 genes, Sectm1a and Sectm1b. Refinement of sorting strategies suggested that both Sectm1 products were induced predominantly in conducting airway epithelial cells. Sectm1 was induced during the early stages of pneumococcal pneumonia, and mutation of NF-kB RelA in epithelial cells did not diminish its expression. Instead, type I IFN signaling was necessary and sufficient for Sectm1 induction in lung epithelial cells, mediated by signal transducer and activator of transcription 1. For target cells, Sectm1a bound to myeloid cells preferentially, in particular Ly6GbrightCD11bbright neutrophils in the infected lung. In contrast, Sectm1a did not bind to neutrophils from uninfected lungs. Sectm1a increased expression of the neutrophil-attracting chemokine CXCL2 by neutrophils from the infected lung. We propose that Sectm1a is an epithelial product that sustains a positive feedback loop amplifying neutrophilic inflammation during pneumococcal pneumonia.

Original languageEnglish
Pages (from-to)407-418
Number of pages12
JournalAmerican journal of respiratory cell and molecular biology
Volume55
Issue number3
DOIs
Publication statusPublished - 2016 Sep
Externally publishedYes

Keywords

  • CXCL2
  • Lung epithelium
  • Neutrophil activation
  • Pneumococcal pneumonia
  • Type I IFNs

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Epithelial cell-derived secreted and transmembrane 1a signals to activated neutrophils during pneumococcal pneumonia'. Together they form a unique fingerprint.

  • Cite this

    Kamata, H., Yamamoto, K., Wasserman, G. A., Zabinski, M. C., Yuen, C. K., Lung, W. Y., Gower, A. C., Belkina, A. C., Ramirez, M. I., Deng, J. C., Quinton, L. J., Jones, M. R., & Mizgerd, J. P. (2016). Epithelial cell-derived secreted and transmembrane 1a signals to activated neutrophils during pneumococcal pneumonia. American journal of respiratory cell and molecular biology, 55(3), 407-418. https://doi.org/10.1165/rcmb.2015-0261OC