Clara cell secretory protein deficiency increases oxidant stress response in conducting airways

Gregory W. Mango, Carl J. Johnston, Susan D. Reynolds, Jacob N. Finkelstein, Charles Plopper, Barry R. Stripp

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Little is known about the molecular basis for differential pulmonary oxidant sensitivity observed between genetically disparate members of the same species. We have generated mice that are deficient in Clara cell secretory protein (CCSP -/-) and that exhibit an oxidant-sensitive phenotype. We characterized the kinetics and distribution of altered stress-response [interleukin-6 (IL-6) and metallothionein (MT)] and epithelial cell-specific [cytochrome P-450 2F2 (CYP2F2)] gene expression to further understand the cellular and molecular basis for altered oxidant sensitivity in 129 strain CCSP -/- mice. Increases in IL-6 and MT mRNA abundance were detected by 2 h of exposure to 1 part/million ozone and preceded reductions in Clara cell CYP2F2 mRNA expression. Despite being qualitatively similar, increases in IL- 6 and MT mRNA expression were enhanced in CCSP -/- mice with respect to coexposed 129 strain wild-type mice. Increased MT mRNA expression, indicative of the stress response, localized to the airway epithelium, surrounding mesenchyme, and endothelium of blood vessels. These results demonstrate a protective role for Clara cells and their secretions and indicate potential genetic mechanisms that may influence susceptibility to oxidant stress.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number2 19-2
StatePublished - Aug 1 1998

Fingerprint

Uteroglobin
Protein Deficiency
Metallothionein
Oxidants
Interleukin-6
Messenger RNA
Cytochrome P-450 Enzyme System
129 Strain Mouse
Ozone
Mesoderm
Endothelium
Blood Vessels
Epithelium
Epithelial Cells
Phenotype
Gene Expression
Lung

Keywords

  • Cytokines
  • Lung injury
  • Metallothionein
  • Ozone
  • Uteroglobin

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Clara cell secretory protein deficiency increases oxidant stress response in conducting airways. / Mango, Gregory W.; Johnston, Carl J.; Reynolds, Susan D.; Finkelstein, Jacob N.; Plopper, Charles; Stripp, Barry R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 275, No. 2 19-2, 01.08.1998.

Research output: Contribution to journalArticle

Mango, Gregory W. ; Johnston, Carl J. ; Reynolds, Susan D. ; Finkelstein, Jacob N. ; Plopper, Charles ; Stripp, Barry R. / Clara cell secretory protein deficiency increases oxidant stress response in conducting airways. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1998 ; Vol. 275, No. 2 19-2.
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