CRTH2 expression on eosinophils from atopic patients

Abstract

Abstract: : Purpose:Prostaglandin (PG) D2, which has been implicated in allergic diseases, is known to have chemotactic activity for eosinophils. The receptor, chemoattractant receptor homologous molecule expressed on Th2 (CRTH2), serves as a receptor for PGD2 and has been reported to mediate PGD2–dependent migration of eosinophils. In the present study, eosinophil chemotaxis induced by PGD2 in atopic patients was compared with that in normal subjects, and the expression of CRTH2 in atopic patients and normal subjects was also investigated. Methods:The subjects in the present study included 12 atopic patients with keratoconjunctivitis (AKC) and 5 normal volunteers. CRTH2 expression on eosinophils was examined using an oligonucleotide array system (GeneChip method), RT–PCR and flow cytometry, and chemotaxis experiments were performed using a modified Boyden chamber technique. Results:GeneChip method, RT–PCR, and flow cytometry analysis revealed that eosinophils in atopic patients showed significantly higher expression of CRTH2 than those in normal subjects. Both PGD2 and the CRTH2 agonist, DK–PGD2 induced chemotaxis of eosinophils in atopic patients. The chemotaxis induced by 100 ng/ml of PGD2 stimulation was significantly higher in severe atopic patients with keratoconjunctivitis (AKC). Conclusions:CRTH2 was expressed more abundantly on eosinophils from atopic patients compared to normal subjects. Eosinophils from atopic patients also exhibited greater chemotaxis to PGD2. This greater reactivity exhibited by eosinophils may be one factor that leads to greater tissue eosinphilia in atopic patients.

Keywords: conjunctivitis • inflammation • eicosanoids