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Neutrophil elastase induces mucus cell metaplasia in mouse lung.

Publication ,  Journal Article
Voynow, JA; Fischer, BM; Malarkey, DE; Burch, LH; Wong, T; Longphre, M; Ho, SB; Foster, WM
Published in: American journal of physiology. Lung cellular and molecular physiology
December 2004

Goblet cell hyperplasia in the superficial airway epithelia is a signature pathological feature of chronic bronchitis and cystic fibrosis. In these chronic inflammatory airway diseases, neutrophil elastase (NE) is found in high concentrations in the epithelial lining fluid. NE has been reported to trigger mucin secretion and increase mucin gene expression in vitro. We hypothesized that chronic NE exposure to murine airways in vivo would induce goblet cell metaplasia. Human NE (50 microg) or PBS saline was aspirated intratracheally by male Balb/c (6 wk of age) mice on days 1, 4, and 7. On days 8, 11, and 14, lung tissues for histology and bronchoalveolar lavage (BAL) samples for cell counts and cytokine levels were obtained. NE induced Muc5ac mRNA and protein expression and goblet cell metaplasia on days 8, 11, and 14. These cellular changes were the result of proteolytic activity, since the addition of an elastase inhibitor, methoxysuccinyl Ala-Ala-Pro-Val chloromethylketone (AAPV-CMK), blocked NE-induced Muc5ac expression and goblet cell metaplasia. NE significantly increased keratinocyte-derived chemokine and IL-5 in BAL and increased lung tissue inflammation and BAL leukocyte counts. The addition of AAPV-CMK reduced these measures of inflammation to control levels. These experiments suggest that NE proteolytic activity initiates an inflammatory process leading to goblet cell metaplasia.

Published In

American journal of physiology. Lung cellular and molecular physiology

DOI

EISSN

1522-1504

ISSN

1040-0605

Publication Date

December 2004

Volume

287

Issue

6

Start / End Page

L1293 / L1302

Related Subject Headings

  • Respiratory System
  • Respiratory Mucosa
  • Mucins
  • Mucin 5AC
  • Mice, Inbred BALB C
  • Mice
  • Metaplasia
  • Male
  • Lung
  • Leukocyte Elastase
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Voynow, J. A., Fischer, B. M., Malarkey, D. E., Burch, L. H., Wong, T., Longphre, M., … Foster, W. M. (2004). Neutrophil elastase induces mucus cell metaplasia in mouse lung. American Journal of Physiology. Lung Cellular and Molecular Physiology, 287(6), L1293–L1302. https://doi.org/10.1152/ajplung.00140.2004
Voynow, Judith A., Bernard M. Fischer, David E. Malarkey, Lauranell H. Burch, Teresa Wong, Malinda Longphre, Samuel B. Ho, and W Michael Foster. “Neutrophil elastase induces mucus cell metaplasia in mouse lung.American Journal of Physiology. Lung Cellular and Molecular Physiology 287, no. 6 (December 2004): L1293–1302. https://doi.org/10.1152/ajplung.00140.2004.
Voynow JA, Fischer BM, Malarkey DE, Burch LH, Wong T, Longphre M, et al. Neutrophil elastase induces mucus cell metaplasia in mouse lung. American journal of physiology Lung cellular and molecular physiology. 2004 Dec;287(6):L1293–302.
Voynow, Judith A., et al. “Neutrophil elastase induces mucus cell metaplasia in mouse lung.American Journal of Physiology. Lung Cellular and Molecular Physiology, vol. 287, no. 6, Dec. 2004, pp. L1293–302. Epmc, doi:10.1152/ajplung.00140.2004.
Voynow JA, Fischer BM, Malarkey DE, Burch LH, Wong T, Longphre M, Ho SB, Foster WM. Neutrophil elastase induces mucus cell metaplasia in mouse lung. American journal of physiology Lung cellular and molecular physiology. 2004 Dec;287(6):L1293–L1302.

Published In

American journal of physiology. Lung cellular and molecular physiology

DOI

EISSN

1522-1504

ISSN

1040-0605

Publication Date

December 2004

Volume

287

Issue

6

Start / End Page

L1293 / L1302

Related Subject Headings

  • Respiratory System
  • Respiratory Mucosa
  • Mucins
  • Mucin 5AC
  • Mice, Inbred BALB C
  • Mice
  • Metaplasia
  • Male
  • Lung
  • Leukocyte Elastase