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.
Watanabe
Maki
M
Department of Dermatology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan.
Satoh
Takahiro
T
Yamamoto
Yoshihiro
Y
Kanai
Yasumasa
Y
Karasuyama
Hajime
H
Yokozeki
Hiroo
H
D000818:Animals; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D054422:Chemokine CCL22 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007073:Immunoglobulin E / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017455:Receptors, IgE / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D019061:src-Family Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism
C515483:Ccl22 protein, mouse; D054422:Chemokine CCL22; D017455:Receptors, IgE; D007073:Immunoglobulin E; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3