Apoptosis in leukocytes induced by UVA in the presence of 8-methoxypsoralen, chlorpromazine or 4,6,4'-trimethylangelicin.

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.

• Authors: Agnieszka Wolnicka-Głubisz, Jolanda M Rijnkels, Tadeusz Sarna, Gerard M J Beijersbergen van Henegouwen
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 68 Issue 2-3 Pg. 65-72 (Nov 2002) ISSN: 1011-1344 [Print] Switzerland
• PMID: 12468199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Furocoumarins
• Photosensitizing Agents
• 4,4',6-trimethylangelicin
• Chlorpromazine
• Methoxsalen

Topics

• Animals
• Apoptosis (drug effects, radiation effects)
• Chlorpromazine (pharmacology)
• Dose-Response Relationship, Drug
• Furocoumarins (pharmacology)
• In Vitro Techniques
• Leukocytes (cytology, radiation effects)
• Male
• Methoxsalen (pharmacology)
• Photosensitizing Agents (pharmacology)
• Rats
• Rats, Wistar
• Ultraviolet Rays