title: Clara cell secretory protein deficiency alters clara cell secretory apparatus and the protein composition of airway lining fluid.
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.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. brs2@pitt.edu
authors.forename: Barry R
authors.initials: BR
authors.lastname: Stripp
authors.forename: Susan D
authors.initials: SD
authors.lastname: Reynolds
authors.forename: Inger-Margrethe
authors.initials: IM
authors.lastname: Boe
authors.forename: Johan
authors.initials: J
authors.lastname: Lund
authors.forename: John H T
authors.initials: JH
authors.lastname: Power
authors.forename: John T
authors.initials: JT
authors.lastname: Coppens
authors.forename: Virginia
authors.initials: V
authors.lastname: Wong
authors.forename: Paul R
authors.initials: PR
authors.lastname: Reynolds
authors.forename: Charles G
authors.initials: CG
authors.lastname: Plopper
mesh_terms: D000818:Animals; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D015180:Electrophoresis, Gel, Two-Dimensional; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000648:ultrastructure; D011506:Proteins / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D014598:Uteroglobin
chemical_list: D004791:Enzyme Inhibitors; D011506:Proteins; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin