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International Immunology Advance Access published online on September 19, 2006
International Immunology, doi:10.1093/intimm/dxl090
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Received May 25, 2006
Accepted August 17, 2006

Article

Trans-basement membrane migration of human basophils: role of matrix metalloproteinase-9

Maho Suzukawa 1, Akiko Komiya 1, Motoyasu Iikura 1, Hiroyuki Nagase 2, Chitose Yoshimura-Uchiyama 3, Hirokazu Yamada 4, Hiroshi Kawasaki 5, Ken Ohta 2, Kouji Matsushima 6, Koichi Hirai 1, Kazuhiko Yamamoto 1, and Masao Yamaguchi 1 *

1 Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
2 Department of Respiratory Medicine, University of Teikyo School of Medicine, Tokyo, Japan
3 Department of Pediatrics, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
4 Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Division of Allergy and Respiratory Medicine, Doai Memorial Hospital, Tokyo, Japan
5 Institute of Medical Science, University of Tokyo, Tokyo, Japan
6 Department of Molecular Preventive Medicine, University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan

* To whom correspondence should be addressed.
Masao Yamaguchi, E-mail: myama-tky{at}umin.ac.jp


  Abstract

In allergic disorders, basophils migrate from the blood stream to inflamed tissue sites. Since trans-basement membrane migration is an important step for local basophil accumulation, we performed a human basophil transmigration assay using a model basement membrane, Matrigel. IL-3 in the upper chamber was critical for basophil trans-basement membrane migration over baseline levels, since none of the chemoattractants placed in the lower chambers induced migration. RANTES, IL-8, 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) and platelet-activating factor (PAF) significantly up-regulated the transmigration of IL-3-treated basophils. Neutralizing experiments indicated the involvement of {beta}2 integrin and matrix metalloproteinase (MMP)-2/9 in basophil transmigration. Real-time quantitative PCR revealed that basophils constitutively expressed transcripts for MMP-9, and at lower levels, MMP-2, but cell-surface expression was only detected for MMP-9. MMP-9 was also detected in the cytoplasm and culture supernatant of the basophils. Treatment with IL-3 up-regulated the surface level of MMP-9 on the basophils. Our results suggest that basophils possess a unique regulatory mechanism for trans-basement membrane migration which is affected by cytokines, chemoattractants, {beta}2 integrin and MMPs, especially MMP-9. MMP-9 may be critically involved in the pathogenesis of local basophil influx in allergic diseases.

Keywords: allergy; asthma; IL-3; transmigration.
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