The murine CCR3 receptor regulates both eosinophilia and hyperresponsiveness in IgE-mediated allergic conjunctivitis.
OBJECTIVE
Allergic conjunctivitis is characterised by early-phase clinical symptoms and late-phase inflammation in the conjunctiva. The role of different chemokine receptors in allergic conjunctivitis, especially during the early-phase reaction, is still unclear. We investigated the importance of CC chemokine receptor (CCR) 3 in a murine model of IgE-mediated allergic conjunctivitis using CCR3-deficient (CCR3(-/-)) mice.


METHODS
Allergic conjunctivitis was initiated in wild-type (WT) and CCR3(-/-) mice by passive transfer of ragweed (RW)-specific IgE, followed by topical challenge with RW in eye drops. Early-phase reactions including clinical symptoms and vascular leakage, as well as late-phase eosinophil infiltration of the conjunctiva were evaluated. The expression of mRNAs in the conjunctiva was quantified by real-time PCR analysis.


RESULTS
The number of infiltrated eosinophils in the conjunctiva following RW challenge, was significantly higher in RW-IgE-sensitised WT mice compared with those sensitised with phosphate-buffered saline for WT, but this was not observed in similarly treated CCR3(-/-) mice. The early-phase clinical symptoms and vascular leakage were also suppressed in CCR3(-/-) mice. The number of conjunctival mast cells were not different between CCR3(-/-) mice and WT mice, and the mRNAs for FcεRІα and the connective tissue-type mast cell proteases were detected in the conjunctiva of both WT and CCR3(-/-) mice. RW-IgE-sensitised CCR3(-/-) mice displayed significantly reduced expression of CCL2, CCL3, and IL-6 compared with WT mice.


CONCLUSIONS
These results demonstrate a direct contribution of CCR3 to both the early-phase reaction and late-phase inflammation during ocular allergy.
Department of Ophthalmology, Kochi Medical School, Oko-cho, Kohasu, Nankoku-city, Kochi 783-8505, Japan. k.fukuda@kochi-u.ac.jp
Ken
K
Fukuda
Chuan-Hui
CH
Kuo
Kei
K
Morohoshi
Fu-Tong
FT
Liu
Santa Jeremy
SJ
Ono
D031164:Ambrosia / Q000276:immunology; D000818:Animals; D003233:Conjunctivitis, Allergic / Q000276:immunology*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000378:metabolism*; D004804:Eosinophils / Q000166:cytology; D006969:Hypersensitivity, Immediate / Q000378:metabolism*; D007073:Immunoglobulin E / Q000276:immunology*; D007958:Leukocyte Count; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D054397:Receptors, CCR3 / Q000502:physiology*
C515351:Ccr3 protein, mouse; D012333:RNA, Messenger; D054397:Receptors, CCR3; D007073:Immunoglobulin E