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Epithelial Cell-Derived Secreted and Transmembrane 1a Signals to Activated
Neutrophils during Pneumococcal Pneumonia
#MMPMID27064756
Kamata H
; Yamamoto K
; Wasserman GA
; Zabinski MC
; Yuen CK
; Lung WY
; Gower AC
; Belkina AC
; Ramirez MI
; Deng JC
; Quinton LJ
; Jones MR
; Mizgerd JP
Am J Respir Cell Mol Biol
2016[Sep]; 55
(3
): 407-18
PMID27064756
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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-?B 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
Ly6G(bright)CD11b(bright) 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.
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