Chemotactic responses of peripheral blood eosinophils to prostaglandin D2 in atopic keratoconjunctivitis

Autor: Hiroshi Fujishima, Kinya Nagata, Hiroyuki Hirai, Naoko Okada, Kenji Matsumoto, Yoji Takano, Hirohisa Saito, Ryoichi Hashida, Kazumi Fukagawa
Rok vydání: 2012
Předmět:
Zdroj: Annals of allergy, asthmaimmunology : official publication of the American College of Allergy, Asthma,Immunology. 111(2)
ISSN: 1534-4436
Popis: Background Eosinophils appear to be key cells in the pathogenesis of conjunctival inflammation in atopic keratoconjunctivitis (AKC). Chemoattractant receptor homologous molecule expressed on T H 2 cells (CRTH2) mediates prostaglandin D 2 (PGD 2 )–dependent migration of eosinophils. However, it is unclear whether CRTH2/PGD 2 -dependent eosinophil migration is upregulated in allergic diseases. Objective To compare the chemotactic responses of peripheral blood eosinophils to prostaglandin D 2 in patients with severe AKC and healthy individuals. Methods We used an enzyme immunoassay system to measure PGD 2 levels in tears and blood samples from healthy individuals and patients with AKC. CRTH2 expression on peripheral blood eosinophils was determined using reverse-transcriptase polymerase chain reaction (RT-PCR), flow cytometry, and an oligonucleotide array system. Chemotaxis experiments were performed using a modified Boyden chamber technique and an optical assay system. Results The PGD 2 concentrations were higher in tears from patients with severe AKC compared with healthy individuals. RT-PCR (severe and mild cases), flow cytometry (mild cases), and GeneChip analyses revealed a significantly higher expression of CRTH2 on peripheral blood eosinophils in patients with AKC than in healthy individuals. PGD 2 and its stable metabolite 13,14-dihydro-15-keto-PGD 2 , a CRTH2 agonist, induced chemotaxis of eosinophils from patients with AKC; chemotaxis was significantly enhanced in eosinophils from patients with severe AKC compared with those from healthy individuals. Conclusion CRTH2 is more abundantly expressed on eosinophils from patients with AKC and promoted PGD 2 -dependent migration to a greater extent than in healthy individuals.
Databáze: OpenAIRE