Basophils plays non-redundant roles in vivo

I. Basophils play non-redundant roles in vivo, that are distinct from those played by mast cells

 Basophils are the least common leukocytes in the peripheral blood and account for only ~0.5% of them. Like mast cells, basophils express the high-affinity IgE receptor Fce RI on their cell surface, and they release chemical mediators such as histamine and leukotriene C4 upon stimulation. Therefore, basophils have often been neglected or considered minor and possibly redundant “circulating mast cells”, and analyzed as a surrogate of the less accessible tissue mast cells. The recent finding that basophils readily generate large quantities of 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.

  We have established allergen-specific IgE transgenic mice as an animal model of allergic disorders (Int. Immunol.,1999). Interestingly, a single subcutaneous injection of multivalent antigens elicited not only immediate- and late-phase ear swelling but also delayed-onset (starting on day 2 post-challenge) ear swelling with massive eosinophil infiltration ( J. Allergy Clin. Immunol., 2003). This was also true for normal mice that were passively sensitized with the IgE..

 Mast cells were essential for the immediate- and late-phase ear swelling but dispensable for the delayed one. T cells were also dispensable for the latter. The delayed-onset allergic inflammation was not developed in FceRI-deficient mice, but it was restored in these mice by transferring FceRI-expressing basophils from normal mice (Immunity, 2005). These findings indicate a novel mechanism of development of chronic allergic inflammation that is induced by basophils through the interaction of antigen, IgE, and FceRI.

 We have recently established a useful mAb, Ba103, that depletes only basophils when administered into mice (Blood, 2007; J. Immunol., 2007). The treatment of mice with Ba103 prior the Ag challenge almost completely abolished the development of the delayed-onset ear swelling. More importantly, the delayed-onset ear swelling was suppressed even when the mice were treated with Ba103 after ear swelling became evident. Even though basophils accounted for only 1-2% of the infiltrating cells in the skin lesions, the Ba103 treatment resulted in drastic reduction in numbers of not only basophils but also eosinophils and neutrophils infiltrating in 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 (Blood, 2007) .

 We are currently analyzing the molecular mechanism underlying the basophil-mediated chronic allergic inflammation by using a panel of engineered mice and the DNA microarray.

References

  1. Establishment of allergen-specific IgE transgenic mice as animal models of allergy
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  2. Chronic allergic inflammation mediated by basophils independently of T cells and mast cells
    Sato, E., Hirahara, K., Wada, Y., Yoshitomi, T., Azuma, T., Matsuoka, K., Kubo, Taya, C., Yonekawa, H., Karasuyama, H. and Shiraishi, A.: Chronic inflammation in skin can be induced in IgE transgenic mice by a single challenge of multivalent antigen. J. Allergy Clin. Immunol. 111: 143-148, 2003. (PubMed)
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    Obata, K., Mukai, K., Tsujimura, Y., Ishiwata, K., Kawano, Y., Minegishi, Y., Watanabe, N., and Karasuyama, H.: Basophils are essential initiators of a novel type of chronic allergic inflammation. Blood 110: 913-920, 2007. (PubMed)
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  3. Regulation of the high affinity receptor IgE (FceRI) expression on the cell surface
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