Primary human alveolar type II epithelial cell chemokine release: Effects of cigarette smoke and neutrophil elastase

Ian R. Witherden, Elizabeth J. Vanden Bon, Peter Goldstraw, Cathy Ratcliffe, Ugo Pastorino, Teresa D. Tetley

Research output: Contribution to journalArticle

Abstract

An early response to cigarette smoke is an influx of leukocytes Into the lung. Alveolar epithelial type II (ATII) cells may contribute by releasing chemokines in response to cigarette smoke and neutrophll elastase (NE). Human ATII cells were purified from normal regions of lungs resected for carcinoma (n = 14). In vitro, these cells exhibited ATII cell characteristics: lamellar bodies, apical microvilli, tight junctions, and expressed surfactant apoprotein C. Basal ATII cell release of five chemokines ranked as follows: monocyte chemotactic protein (MCP)-1 > interleukin (IL)-8 > growth-related oncogene (GRO)-α > macrophage inflammatory protein (MIP)-1α > regulated on activation, normal T cell expressed and secreted (RANTES). MIP-1α and RANTES were often not detectable. After stimulation with a mixture of lipopolysaccharide/endotoxin (LPS), tumor necrosis factor-α, IL-1β, and IFN-γ, MCP-1 and IL-8 secretion rose 4-6-fold, whereas GRO-α rose 25-fold. NE stimulated IL-8 mRNA expression, and 10nM NE stimulated IL-8 secretion; however, 100nM NE caused a decrease in extracellular IL-8, MCP-1, and GRO-α, attributed to proteolysts. Cigarette smoke extract (CSE) Inhibited IL-8 mRNA expression and release of all chemokines. Clutathione protected against the effects of CSE, suggesting oxidative mechanisms. GRO-α, important in growth and repair, was sensitive to both stimulation, by LPS:cytokines, and inhibition, by CSE. Thus, contrary to the original hypothesis, high concentrations of NE and CSE resulted in reduced extracellular chemokine levels. We hypothesize that reduced ATII cell-derived chemokine levels compromise alveolar repair, contributing to cigarette smoke-induced alveolar damage and emphysema.

Original languageEnglish
Pages (from-to)500-509
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume30
Issue number4
DOIs
Publication statusPublished - Apr 2004

Fingerprint

Alveolar Epithelial Cells
Leukocyte Elastase
Chemokines
Smoke
Tobacco Products
Interleukin-8
Pancreatic Elastase
Oncogenes
Chemokine CCL2
Macrophage Inflammatory Proteins
Growth
T-cells
Endotoxins
Lipopolysaccharides
Repair
Chemical activation
Apolipoproteins C
T-Lymphocytes
Lung
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Primary human alveolar type II epithelial cell chemokine release : Effects of cigarette smoke and neutrophil elastase. / Witherden, Ian R.; Vanden Bon, Elizabeth J.; Goldstraw, Peter; Ratcliffe, Cathy; Pastorino, Ugo; Tetley, Teresa D.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 30, No. 4, 04.2004, p. 500-509.

Research output: Contribution to journalArticle

Witherden, Ian R. ; Vanden Bon, Elizabeth J. ; Goldstraw, Peter ; Ratcliffe, Cathy ; Pastorino, Ugo ; Tetley, Teresa D. / Primary human alveolar type II epithelial cell chemokine release : Effects of cigarette smoke and neutrophil elastase. In: American Journal of Respiratory Cell and Molecular Biology. 2004 ; Vol. 30, No. 4. pp. 500-509.
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