Enhancement of basophil apoptosis by olopatadine and theophylline.
Regulation of basophil survival is an important aspect in the pathogenesis of allergic inflammation associated with local accumulation of basophils. However, pharmacologic modulation of basophil survival is largely unknown except for the apoptosis-enhancing effect of glucocorticoids. We tested the effects of two anti-allergic and anti-asthmatic drugs, olopatadine and theophylline, on basophil survival. Basophils were highly purified from normal human peripheral blood. Apoptosis was analyzed by flow cytometry using annexin V staining or another staining method that detected alterations in the mitochondrial transmembrane potential. In addition to the conventional method using annexin V, basophil apoptosis was successfully established by analysis of the mitochondrial transmembrane potential. Olopatadine decreased the number of live basophils, and they induced apoptosis of basophils during culture. The decline in live basophils was induced by olopatadine even when low doses of IL-3 were included in the culture medium. Theophylline also affected basophil apoptosis and induced a decrease in the number of live basophils. Basophil apoptosis was enhanced by both olopatadine and theophylline. This effect may partly explain the pharmacologic basis of why these drugs are effective on allergic diseases.
Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Ayako
A
Kawakami
Maho
M
Suzukawa
Rikiya
R
Koketsu
Akiko
A
Komiya
Ken
K
Ohta
Kazuhiko
K
Yamamoto
Masao
M
Yamaguchi
D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001491:Basophils / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018929:Cell Culture Techniques; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects* / Q000276:immunology; D003990:Dibenzoxepins / Q000276:immunology / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000188:drug therapy / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D000069605:Olopatadine Hydrochloride; D013806:Theophylline / Q000276:immunology / Q000494:pharmacology*
D003990:Dibenzoxepins; D000069605:Olopatadine Hydrochloride; D013806:Theophylline