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Am J Physiol Lung Cell Mol Physiol 296: L30-L36, 2009. First published October 17, 2008; doi:10.1152/ajplung.00026.2008
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Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation

Masakata Yoshioka,1,2,* Hironori Sagara,4,* Fumiyuki Takahashi,1,2,* Norihiro Harada,1,2,3 Kazuto Nishio,5 Akio Mori,6 Hiroko Ushio,3 Kazue Shimizu,1,2 Takenori Okada,4 Mayumi Ota,4 Yoichi M. Ito,7 Osamu Nagashima,1,2,3 Ryo Atsuta,1,2,3 Toshihiro Suzuki,8 Takeshi Fukuda,4 Yoshinosuke Fukuchi,1,2 and Kazuhisa Takahashi1,2

1Department of Respiratory Medicine, 2Research Institute for Diseases of Old Ages, and 3Atopy (Allergy) Research Center, Juntendo University School of Medicine, Bunkyo-Ku, Tokyo; 4Department of Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine, Tochigi; 5Department of Genome Biology, Kinki University School of Medicine, Osaka; 6Clinical Research Center for Allergy and Rheumatology, National Sagamihara Hospital, Kanagawa; 7Department of Biostatistics, School of Public Health, The University of Tokyo, Tokyo; and 8Department of Analytical Biochemistry, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan

Submitted 14 January 2008 ; accepted in final form 14 October 2008

Multidrug resistance-associated protein 1 (MRP1) is a cysteinyl leukotriene (CysLT) export pump expressed on mast cells. CysLTs are crucial mediators in allergic airway disease. However, biological significance of MRP1 in allergic airway inflammation has not yet been elucidated. In this study, we sensitized wild-type control mice (mrp1+/+) and MRP1-deficient mice (mrp1–/–) to ovalbumin (OVA) and challenged them with OVA by aerosol. Airway inflammation and goblet cell hyperplasia after OVA exposure were reduced in mrp1–/– mice compared with mrp1+/+ mice. Furthermore, CysLT levels in bronchoalveolar lavage fluid (BALF) from OVA-exposed mrp1–/– mice were significantly lower than those from OVA-exposed mrp1+/+ mice. Levels of OVA-specific IgE, IL-4, and IL-13 in BALF were also decreased in OVA-exposed mrp1–/– mice. IgE-mediated release of CysLTs from murine bone marrow-derived mast cells was markedly impaired by MRP1 deficiency. Our results indicate that MRP1 plays an important role in the development of allergic airway inflammation through regulation of IgE-mediated CysLT export from mast cells.

cysteinyl leukotrienes; mast cell


Address for reprint requests and other correspondence: M. Yoshioka, Dept. of Respiratory Medicine, Juntendo Univ. School of Medicine, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan (e-mail: seigo{at}juntendo.ac.jp)






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