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Published ahead of print on June 10, 2004, doi:10.1165/rcmb.2004-0060OC

Am. J. Respir. Cell Mol. Biol., Volume 31, Number 4, October 2004, 382-394

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Submitted on February 20, 2004
Revised on June 8, 2004

Mucin Is Produced by Clara Cells in the Proximal Airways of Antigen Challenged Mice

Christopher M Evans1*, Olatunji W Williams2, Michael J Tuvim2, Rupesh Nigam2, George P Mixides2, Michael R Blackburn3, Fracesco J DeMayo4, Alan R Burns2, Charlotte Smith5, Susan D Reynolds5, Barry R Stripp5, and Burton F Dickey6

1 Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Department of Pulmonary Medicine, MD Anderson Cancer, Houston, TX, USA, 2 Department of Medicine, Baylor College of Medicine, Houston, TX, USA, 3 Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, TX, USA, 4 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA, 5 Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA, USA, 6 Department of Pulmonary Medicine, MD Anderson Cancer, Houston, TX, USA

* To whom correspondence should be addressed. E-mail: cevans{at}bcm.tmc.edu.

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 (~40%) and non-ciliated (~60%) epithelial cells line the airways, and >95% of the non-ciliated cells are Clara cells that contain Clara cell secretory protein (CCSP). Mucous cells comprise <5% of the non-ciliated 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 non-ciliated/non-basal 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 immunohisotchemically 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.




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