An In Vitro Approach to Drug Photoallergy: Use of Drug-directed Antibodies to Assess Photobinding of Non-steroidal Anti-inflammatories to Skin Cells.
Photobinding of drugs to biomolecules constitutes the early key event in the onset of photoallergy. This process generally involves excitation of the drug to an excited triplet state, which in turn can interact with cell constituents leading, in the case of proteins, to the formation of covalent photoadducts. The resulting photoantigens may trigger an immune response. In the present communication, we report the use of drug-directed antibodies to detect photoadduct formation in skin cells. This has been exemplified with tiaprofenic acid and suprofen as model compounds (two well known photoallergens) and human fibroblasts as representative skin cells. Upon irradiation of cells in the presence of these non-steroidal anti-inflammatories, time-dependent photoadduct formation was observed. This occurred predominantly at the cell membrane level. Most interestingly, the immunogenicity of cell photoadducts could be demonstrated by injection of Balb/c mouse fibroblasts into immunologically identical syngenic animals, where they triggered an immune response, as evidenced by the formation of specific antibodies and sensitized T-cells.
Miranda
M A
MA
Departamento de Quimica/Instituto de Tecnologia Quimica UPV-CSIC, Universidad Politécnica de Valencia, Valencia and Centro de Investigación, Hospital Universitario La Fe (SVS), Valencia, Spain.
Sarabia
Z
Z
Hernández
D
D
Morera
I M
IM
Gómez-Lechón
M J
MJ
Castell
J V
JV