TY - JOUR
T1 - Differential expression of chitinases identify subsets of murine airway epithelial cells in allergic inflammation
AU - Homer, Robert J.
AU - Zhu, Zhou
AU - Cohn, Lauren
AU - Chun, Gun Lee
AU - White, Wendy I.
AU - Chen, Suping
AU - Elias, Jack A.
PY - 2006
Y1 - 2006
N2 - 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 down-regulation 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.
AB - 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 down-regulation 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.
KW - Airway epithelial differentiation
KW - Airway remodeling
KW - Mucus
UR - http://www.scopus.com/inward/record.url?scp=33748418032&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748418032&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00364.2005
DO - 10.1152/ajplung.00364.2005
M3 - Article
C2 - 16556727
AN - SCOPUS:33748418032
SN - 1040-0605
VL - 291
SP - L502-L511
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 3
ER -