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-Induced Resolution of Allergen- Induced Mucus Cell Metaplasia1
* Lovelace Respiratory Research Institute, Albuquerque, NM 87108;
Respiratory Research Group, University of Calgary, Calgary, Alberta, Canada; and
Aventis Pharmaceutical, Bridgewater, NH 08870
Allergic airway responses cause proliferation of epithelial cells
and mucus cell metaplasia (MCM), and the resolution of MCM involves
reduction of cell numbers. The role of inflammation and apoptosis on
this process was investigated in P-selectin +/+ and -/- mice
sensitized and challenged with OVA by analyzing the expression and the
role of regulators of apoptosis in metaplastic mucus cells. No
differences were observed in MCM at 5 days of allergen exposure between
+/+ and -/- mice, despite reduced IL-13 levels in -/- mice.
Although IL-4 levels were similar in both -/- and +/+ mice, IL-13 and
IL-5 levels had decreased and IFN-
levels were increased earlier in
-/- compared with +/+ mice. MCM levels were decreased 4-fold at 7
days of allergen exposure in -/- mice and at 15 days in +/+ mice. The
percentage of Bax-expressing mucus cells increased significantly at 7
days in -/- mice and at 10 days in +/+ mice. The Bax-positive mucus
cells exhibited caspase-specific cleavage of cytokeratin 18. IFN-
caused Bax expression in IL-13-induced MCM in microdissected airway
cultures. MCM remained significantly elevated in Bax -/- mice
following 15 days of allergen exposure compared with +/+ mice, while
the number of eosinophils was reduced in both Bax +/+ and -/- mice at
15 days. Together, these data demonstrate that reduced IL-13 levels
were sufficient to elicit maximum MCM, that IFN- induces Bax in
metaplastic mucus cells, and that Bax plays a critical role in the
resolution of MCM, but not in the resolution of
eosinophils.
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