The murine CCR3 receptor regulates both eosinophilia and hyperresponsiveness in IgE-mediated allergic conjunctivitis.

Abstract

BACKGROUND/AIMS:

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.

• Authors: Ken Fukuda, Chuan-Hui Kuo, Kei Morohoshi, Fu-Tong Liu, Santa Jeremy Ono
• Journal: The British journal of ophthalmology (Br J Ophthalmol) Vol. 96 Issue 8 Pg. 1132-6 (Aug 2012) ISSN: 1468-2079 [Electronic] England
• PMID: 22694967 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Ccr3 protein, mouse
• RNA, Messenger
• Receptors, CCR3
• Immunoglobulin E

Topics

• Ambrosia (immunology)
• Animals
• Conjunctivitis, Allergic (immunology)
• Disease Models, Animal
• Eosinophilia (metabolism)
• Eosinophils (cytology)
• Hypersensitivity, Immediate (metabolism)
• Immunoglobulin E (immunology)
• Leukocyte Count
• Mice
• Mice, Knockout
• RNA, Messenger (metabolism)
• Real-Time Polymerase Chain Reaction
• Receptors, CCR3 (physiology)