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Overproduction of IgE Induces Macrophage-Derived Chemokine (CCL22) Secretion from Basophils

Maki Watanabe^1,*, Takahiro Satoh^1,2,*, Yoshihiro Yamamoto^*, Yasumasa Kanai^*, Hajime Karasuyama and Hiroo Yokozeki^*

^* Department of Dermatology, and Department of Immune Regulation, Tokyo Medical and Dental University Graduate School, Tokyo, Japan

Macrophage-derived chemokine (MDC) CCL22 is a potent chemoattractant for Th2 cells and has been implicated in Th2-predominant allergic inflammation. In the present study, we demonstrated that basophils produce MDC in response to monomeric IgE. In trinitrophenyl (TNP)-IgE transgenic mice, serum levels of MDC were persistently higher than in wild-type mice. The i.v. administration of TNP-specific IgE to wild-type mice transiently induced an elevation in serum MDC, which appeared to be mediated by FcRI, as no increase in serum MDC was observed after IgE administration in FcR (–/–) mice. However, the IgE-mediated increase in MDC was observed in mast cell-deficient mice. Freshly isolated bone marrow cells and bone marrow-derived basophils secreted MDC in response to TNP-IgE without Ag stimulation. Furthermore, MDC production was not observed in bone marrow-derived basophils isolated from FcR (–/–) mice. IgE activated Lyn and ERK 1/2 in bone marrow-derived basophils. Treatment of TNP-IgE transgenic mice with a basophil-depletion Ab (Ba103) resulted in decreased serum MDC levels. Thus, IgE appears to be capable of stimulating basophils to produce MDC in the absence of a specific Ag, which may contribute to IgE-mediated and/or Th2-predominant allergic inflammation.

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¹ M.W. and T.S. contributed equally to this work.

² Address correspondence and reprint requests to Dr. Takahiro Satoh, Department of Dermatology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Japan. E-mail address: tasa-1688.derm{at}tmd.ac.jp

³ Abbreviations used in this paper: MDC, macrophage-derived chemokine; ITR, immediate type reaction; LPR, late phase response; TNP, trinitrophenyl; BMBa, bone marrow-derived basophil; BMMC, bone marrow-derived mast cell.