Suppression of eosinophilic airway inflammation by treatment with alpha-galactosylceramide |
| |
Authors: | Morishima Yuko Ishii Yukio Kimura Toru Shibuya Akira Shibuya Kazuko Hegab Ahmed E Iizuka Takashi Kiwamoto Takumi Matsuno Yosuke Sakamoto Tohru Nomura Akihiro Taniguchi Masaru Sekizawa Kiyohisa |
| |
Affiliation: | Department of Pulmonary Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. mk01a231@md.tsukuba.ac.jp |
| |
Abstract: | To clarify the essential role of NKT cells in allergy, we investigated the contribution of NKT cells to the pathogenesis of eosinophilic airway inflammation using alpha-galactosylceramide (alpha-GalCer), a selective ligand for NKT cells. Although continuous administration of alpha-GalCer during ovalbumin (OVA) sensitization increased OVA-specific IgE levels and worsened eosinophil inflammation, a single administration of alpha-GalCer at the time of OVA challenge completely prevented eosinophilic infiltration in wild-type mice. This inhibitory effect of alpha-GalCer was associated with a decrease in airway hyperresponsiveness, an increase in IFN-gamma, and decreases in IL-4, IL-5 and IL-13 levels in the bronchoalveolar lavage fluids. Analysis of lung lymphocytes revealed that production of IFN-gamma increased in NK cells, but not in T or NKT cells, following alpha-GalCer administration. Induction of vascular cell adhesion molecule-1 in the lungs of wild-type mice was also significantly attenuated by treatment with alpha-GalCer. These effects of alpha-GalCer were abrogated in J alpha281-/- mice, which lack NKT cells, and in wild-type mice treated with anti-IFN-gamma Ab. Hence, our data indicate that alpha-GalCer suppresses allergen-induced eosinophilic airway inflammation, possibly by inducing a Th1 bias that results in inhibition of eosinophil adhesion to the lung vessels. |
| |
Keywords: | Eosinophil NKT cell α‐galactosylceramide IFN‐γ VCAM‐1 |
本文献已被 PubMed 等数据库收录! |
|