Clara cell secretory protein deficiency alters Clara cell secretory apparatus and the protein composition of airway lining fluid

Barry R. Stripp, Susan D. Reynolds, Inger Margrethe Boe, Johan Lund, John H.T. Power, John T. Coppens, Virginia Wong, Paul R. Reynolds, Charles Plopper

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Clara cells represent the predominant secretory cell within distal conducting airways of mammals and exhibit functional alterations with chronic lung disease. We previously demonstrated that Clara cell secretory protein (CCSP) deficiency results in enhanced susceptibility to environmental agents. The present study was undertaken to define changes in Clara cell secretory function associated with CCSP deficiency in knockout mice. Comparative morphometry of Clara cell ultrastructure revealed dramatic alterations in secretory apparatus between wild-type (WT) and CCSP knockout (CCSP-/-) mice. Secretory granules, which occupy greater than 2% of Clara cell cytoplasmic volume in WT mice, were completely absent among Clara cells of CCSP-/- mice. Moreover, Clara cells of CCSP-/- mice exhibited a > 95% reduction in rough endoplasmic reticulum and alterations to Golgi apparatus, relative to WT controls. Ultrastructural perturbations to Clara cells were associated with altered protein composition of airway lining fluid as revealed by two-dimensional gel analysis of bronchoalveolar lavage proteins, but were not associated with altered abundance or secretion of CC26, another Clara cell secretory protein. We conclude that CCSP is required for the appearance of Clara cell secretory granules and that functional changes to Clara cells that result from CCSP deficiency lead to alterations in the composition of epithelial lining fluid.

Original languageEnglish (US)
Pages (from-to)170-178
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume27
Issue number2
DOIs
StatePublished - Jan 1 2002
Externally publishedYes

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Uteroglobin
Protein Deficiency
Linings
Fluids
Chemical analysis
Proteins
Secretory Vesicles
Pulmonary diseases
Mammals
Rough Endoplasmic Reticulum
Gels
Golgi Apparatus
Bronchoalveolar Lavage
Cell Size
Knockout Mice
Lung Diseases
Chronic Disease

ASJC Scopus subject areas

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

Cite this

Clara cell secretory protein deficiency alters Clara cell secretory apparatus and the protein composition of airway lining fluid. / Stripp, Barry R.; Reynolds, Susan D.; Boe, Inger Margrethe; Lund, Johan; Power, John H.T.; Coppens, John T.; Wong, Virginia; Reynolds, Paul R.; Plopper, Charles.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 27, No. 2, 01.01.2002, p. 170-178.

Research output: Contribution to journalArticle

Stripp, Barry R. ; Reynolds, Susan D. ; Boe, Inger Margrethe ; Lund, Johan ; Power, John H.T. ; Coppens, John T. ; Wong, Virginia ; Reynolds, Paul R. ; Plopper, Charles. / Clara cell secretory protein deficiency alters Clara cell secretory apparatus and the protein composition of airway lining fluid. In: American Journal of Respiratory Cell and Molecular Biology. 2002 ; Vol. 27, No. 2. pp. 170-178.
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