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(American Journal of Pathology. 2006;169:795-805.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060079

Platelet-Activating Factor Is Crucial in Psoralen and Ultraviolet A-Induced Immune Suppression, Inflammation, and Apoptosis

Peter Wolf*{dagger}, Dat X. Nghiem{dagger}{ddagger}, Jeffrey P. Walterscheid{dagger}{ddagger}, Scott Byrne{dagger}, Yumi Matsumura{dagger}, Yasuhiro Matsumura{dagger}, Cora Bucana{dagger}§, Honnavara N. Ananthaswamy{dagger}{ddagger} and Stephen E. Ullrich{dagger}{ddagger}

From the Department of Dermatology,* Research Unit for Photodermatology, Medical University Graz, Graz, Austria; the Departments of Immunology{dagger} and Cancer Biology,§ The University of Texas M.D. Anderson Cancer Center, Houston, Texas; and The Graduate School for Biomedical Sciences,{ddagger} Houston, Texas

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA’s mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects.




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