Ablation of type I hypersensitivity in experimental allergic conjunctivitis by eotaxin-1/CCR3 blockade.
The immune response is regulated, in part, by effector cells whose activation requires multiple signals. For example, T cells require signals emanating from the T cell antigen receptor and co-stimulatory molecules for full activation. Here, we present evidence indicating that IgE-mediated hypersensitivity reactions in vivo also require cognate signals to activate mast cells. Immediate hypersensitivity reactions in the conjunctiva are ablated in mice deficient in eotaxin-1, despite normal numbers of tissue mast cells and levels of IgE. To further define the co-stimulatory signals mediated by chemokine receptor 3 (CCR3), an eotaxin-1 receptor, effects of CCR3 blockade were tested with an allergic conjunctivitis model and in ex vivo isolated connective tissue-type mast cells. Our results show that CCR3 blockade significantly suppresses allergen-mediated hypersensitivity reactions as well as IgE-mediated mast cell degranulation. We propose that a co-stimulatory axis by CCR3, mainly stimulated by eotaxin-1, is pivotal in mast cell-mediated hypersensitivity reactions.
Miyazaki
Dai
D
Division of Ophthalmology and Visual Science, Tottori University Faculty of Medicine, Tottori, Japan. dm@grape.med.tottori-u.ac.jp
Nakamura
Takao
T
Ohbayashi
Masaharu
M
Kuo
Chuan Hui
CH
Komatsu
Naoki
N
Yakura
Keiko
K
Tominaga
Takeshi
T
Inoue
Yoshitsugu
Y
Higashi
Hidemitsu
H
Murata
Meguru
M
Takeda
Shuzo
S
Fukushima
Atsuki
A
Liu
Fu-Tong
FT
Rothenberg
Marc E
ME
Ono
Santa Jeremy
SJ
D000485:Allergens / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D002415:Cats; D015550:Cell Degranulation / Q000276:immunology; D054413:Chemokine CCL11 / Q000276:immunology* / Q000378:metabolism; D003228:Conjunctiva / Q000276:immunology / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D007073:Immunoglobulin E / Q000097:blood; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054397:Receptors, CCR3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D014611:Vaccination
D000485:Allergens; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D006023:Glycoproteins; D054397:Receptors, CCR3; D007073:Immunoglobulin E; C059296:Fel d 1 protein, Felis domesticus