Crth2 Expression On Eosinophils From Atopic Patients

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. We have hyposesized that higher number of CRTH2 on eosinophils may be one of the pathogens of atopic disease. In the present study, the expression of CRTH2 on eosinophils in atopic patients compared to normal subjects was investigated, and the eosinophil chemotaxis induced by PGD₂ in atopic patients was also compared with that in normal subjects.

Methods: : The subjects in the present study included 12 atopic patients and 5 normal volunteers. CRTH2 expression on eosinophils was performed using an oligonucleotide array system, 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 and normal. The chemotaxis induced by PGD₂ stimulation was significantly higher in severe atopic patients with keratoconjunctivitis (AKC) than that of normal subjects in a dose dependent manner.

Conclusions: : CRTH2 is expressed more abundantly in atopic patients’ eosinophils and that these cells respond to a greater extent to dose dependent concentrations of PGD₂.

Keywords: conjunctivitis • clinical (human) or epidemiologic studies: biostatistics/epidemiology methodology • conjunctiva