Augmentation of apoptosis in bronchial exuded rat eosinophils by cyclosporin A.
The effect of cyclosporin A on apoptosis in eosinophils was examined to clarify the inhibitory mechanisms of cyclosporin A on allergen-induced eosinophilia in the airway. Eosinophils in bronchoalveolar lavage fluid from sensitized rats after inhaling an allergen were used. More than 50% of the eosinophils that died spontaneously by apoptosis within 24 hour incubation in RPMI 1640 medium contained 10% fetal calf serum. The addition of cyclosporin A or dexamethasone significantly enhanced the eosinophils apoptosis at concentrations of more than 0.1 microM. Apoptosis in eosinophils was considerably suppressed in the presence of culture supernatant of activated splenocytes as a source of various cytokines. Even in the presence of culture supernatant of activated splenocytes, cyclosporin A or dexamethasone facilitated apoptosis in eosinophils. These results suggest that apoptotic death of activated eosinophils is augmented with cyclosporin A and that accelerated apoptosis in eosinophils of the airway may account for the inhibitory effect of cyclosporin A on eosinophilia.
Kitagaki
K
K
Department of Pharmacology, Sandoz Tsukuba Research Institute, Ibaraki, Japan.
Niwa
S
S
Hoshiko
K
K
Nagai
H
H
Hayashi
S
S
Totsuka
T
T
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects; D008213:Lymphocyte Activation; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D011914:Rats, Inbred BN; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D018927:Anti-Asthmatic Agents; D016572:Cyclosporine; D010047:Ovalbumin