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This Article Full Text Full Text (PDF) All Versions of this Article: 291/3/L502    most recent 00364.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Homer, R. J. Articles by Elias, J. A. Search for Related Content PubMed PubMed Citation Articles by Homer, R. J. Articles by Elias, J. A.

Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation

¹Department of Pathology, Yale University School of Medicine and Pathology and Laboratory Medicine Service, Veterans Affairs Connecticut HealthCare System, West Haven; ²Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut; and ³MedImmune, Gaithersburg, Maryland

Submitted 18 August 2005 ; accepted in final form 9 March 2006

The mammalian chitinase family includes members both with and without enzymatic activity against chitin, a product of fungal cell walls, exoskeletons of crustaceans and insects, and the microfilarial sheaths of parasitic nematodes. Two members of that family, Ym1 and acidic mammalian chitinase (AMCase), are strongly upregulated in pulmonary T helper (Th) 2 inflammation but not in Th1 inflammation. The sites of expression of these products are incompletely known. We show here that, in two different models of Th2 inflammation, Ym1 and AMCase are mutually exclusively expressed in proximal vs. distal airway epithelium, respectively, whereas both are expressed in alveolar macrophages. This regional difference along the airway corresponds to the previously noted distinction between mucus positive proximal cells and mucus negative distal cells under the same conditions. Among distal cells, AMCase colocalizes with epithelial cells expressing the Clara cell marker Clara cell secretory protein. These AMCase-expressing cells retain expression of FOXA2, a transcription factor whose downregulation in association with IL-13 signaling has previously been associated with production of mucus in proximal airway epithelial cells. These results provide evidence that secretory cells of proximal and distal airways undergo fundamentally different gene expression programs in response to allergic inflammation. Furthermore, AMCase provides the first positive molecular marker of distal Clara cell secretory protein-expressing cells under these conditions.

airway epithelial differentiation; mucus; airway remodeling

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