Mucin is produced by clara cells in the proximal airways of antigen-challenged mice.
Airway mucus hypersecretion is a prominent feature of many obstructive lung diseases. We thus determined the ontogeny and exocytic phenotype of mouse airway mucous cells. In naive mice, ciliated (approximately 40%) and nonciliated (approximately 60%) epithelial cells line the airways, and > 95% of the nonciliated cells are Clara cells that contain Clara cell secretory protein (CCSP). Mucous cells comprise < 5% of the nonciliated cells. After sensitization and a single aerosol antigen challenge, alcian blue-periodic acid Schiff's positive mucous cell numbers increase dramatically, appearing 6 h after challenge (21% of nonciliated/nonbasal cells), peaking from Days 1-7 (99%), and persisting at Day 28 (65%). Throughout the induction and resolution of mucous metaplasia, ciliated and Clara cell numbers identified immunohistochemically change only slightly. Intracellular mucin content peaks at Day 7, and mucin expression is limited specifically to a Clara cell subset in airway generations 2-4 that continue to express CCSP. Functionally, Clara cells are secretory cells that express the regulated exocytic marker Rab3D and, in antigen-challenged mice, rapidly secrete mucin in response to inhaled ATP in a dose-dependent manner. Thus, Clara cells show great plasticity in structure and secretory products, yet have molecular and functional continuity in their identity as specialized apical secretory cells.
Evans
Christopher M
CM
Pulmonary Medicine, M.D. Anderson Cancer Center, 2121 West Holcombe Blvd., Houston, TX 77030, USA. cevans@mdanderson.org
Williams
Olatunji W
OW
Tuvim
Michael J
MJ
Nigam
Rupesh
R
Mixides
George P
GP
Blackburn
Michael R
MR
DeMayo
Francesco J
FJ
Burns
Alan R
AR
Smith
Charlotte
C
Reynolds
Susan D
SD
Stripp
Barry R
BR
Dickey
Burton F
BF
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001980:Bronchi / Q000166:cytology* / Q000378:metabolism; D002923:Cilia / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology*; D005260:Female; D007124:Immunoenzyme Techniques; D008679:Metaplasia / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D020545:Respiratory Mucosa / Q000166:cytology*; D014598:Uteroglobin / Q000378:metabolism*; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; C556390:Scgb1a1 protein, mouse; D000255:Adenosine Triphosphate; D014598:Uteroglobin; C116709:Rab3b protein, mouse; C116711:Rab3d protein, mouse; D020692:rab3 GTP-Binding Proteins