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Apoptosis in leukocytes induced by UVA in the presence of 8-methoxypsoralen, chlorpromazine or 4,6,4'-trimethylangelicin.
- Source :
-
Journal of photochemistry and photobiology. B, Biology [J Photochem Photobiol B] 2002 Nov; Vol. 68 (2-3), pp. 65-72. - Publication Year :
- 2002
-
Abstract
- Although 8-methoxypsoralen (8-MOP) has been successfully used in extracorporeal photochemotherapy (ECP) of several T cell-mediated diseases, the exact mechanism of the drug therapeutic action has not been established. We have studied in vitro apoptotic activity of 8-MOP, and for comparison of 4,6,4'-trimethylangelicin (TMA) and chlorpromazine (CPZ) as alternative photosensitizers for potential use in photopheresis. However, while 8-MOP and CPZ are known for their immune suppressive activity, TMA does not exhibit such an activity in an animal model for ECP. Apoptosis and necrosis were measured in both Jurkat cells and primary rat leukocytes under conditions comparable to those used in the animal model to suppress contact hypersensitivity (CHS). Cells were irradiated with UVA (200 kJ/m(2)) after treatment with 8-MOP, CPZ or TMA (300 ng/ml). Flow cytometric analysis (annexin-V-FLUOS/propidium iodide) and fluorescence microscopy examinations, using acridine orange/propidium iodide, indicated that the number of cells undergoing apoptosis or necrosis increased significantly after 24 h following treatment. Similar results were observed irrespective of the cell type and photosensitizer used. The results of the present study, combined with previous observations with the animal model for ECP, suggest that apoptosis is not likely to be a critical step in the cascade of events leading to immunosuppression.
- Subjects :
- Animals
Apoptosis drug effects
Dose-Response Relationship, Drug
In Vitro Techniques
Male
Photosensitizing Agents pharmacology
Rats
Rats, Wistar
Apoptosis radiation effects
Chlorpromazine pharmacology
Furocoumarins pharmacology
Leukocytes cytology
Leukocytes radiation effects
Methoxsalen pharmacology
Ultraviolet Rays
Subjects
Details
- Language :
- English
- ISSN :
- 1011-1344
- Volume :
- 68
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- Journal of photochemistry and photobiology. B, Biology
- Publication Type :
- Academic Journal
- Accession number :
- 12468199
- Full Text :
- https://doi.org/10.1016/s1011-1344(02)00332-9