Overproduction of IgE induces macrophage-derived chemokine (CCL22) secretion from basophils.

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 Fc epsilonRI, as no increase in serum MDC was observed after IgE administration in FcRgamma (-/-) 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 FcRgamma (-/-) 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.