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Blood, 1 August 2007, Vol. 110, No. 3, pp. 913-920.
Prepublished online as a Blood First Edition Paper on April 4, 2007; DOI 10.1182/blood-2007-01-068718.
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IMMUNOBIOLOGY
Basophils are essential initiators of a novel type of chronic allergic inflammation
Kazushige Obata1,
Kaori Mukai1,
Yusuke Tsujimura1,
Kenji Ishiwata2,
Yohei Kawano1,
Yoshiyuki Minegishi1,
Naohiro Watanabe2, and
Hajime Karasuyama1
1 Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Bunkyo-ku, Tokyo;
2 Department of Tropical Medicine, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan
Basophils represent less than 1% of peripheral blood leukocytes and have often been considered as minor and possibly redundant circulating mast cells. The recent finding that basophils readily generate large quantities of T helper 2 (Th2) cytokines such as IL-4 provided new insights into the possible role of basophils in allergic disorders and immunity to pathogens. However, in-depth studies on basophils, particularly their functions in vivo, have been hampered by the lack of appropriate animal models, such as mutant animals deficient only in basophils. Here, we established a mAb that reacted with mouse basophils and depleted them when administered in vivo. The mAb treatment of mice did not show any significant effect on classical allergic reactions such as passive cutaneous anaphylaxis and contact hypersensitivity. In contrast, it completely abolished the development of IgE-mediated chronic allergic dermatitis that is characterized by massive eosinophil infiltration, even though basophils accounted for only approximately 2% of the infiltrates. The treatment during the progression of the dermatitis resulted in drastic reduction in numbers of infiltrating eosinophils and neutrophils, concomitantly with elimination of basophils from the skin lesions. Thus, basophils play a pivotal role in the development of IgE-mediated chronic allergic inflammation, as an initiator rather than as an effector.
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