Degranulation of mast cells and inhibition of the response to secretory agents by phototoxic compounds and ultraviolet radiation.
The symptoms of cutaneous phototoxicity from coal tar compounds and the nonsteroidal anti-inflammatory drug benoxaprofen are characterized by wheal and flare formation which is mediated by histamine released from dermal mast cells. Rat serosal mast cells were used as an in vitro model system to study the direct effect of phototoxic compounds on mast cell degranulation. The coal tar compounds studied included acridine and pyrene. Combined exposure of cells to acridine and UVA (320 to 400 nm) radiation caused mast cells to degranulate, as assayed by the release of [3H]serotonin. Maximum [3H]serotonin release (70 to 80%) was obtained with 50 microM acridine and 300 kJ/m2 UVA. Pyrene (25 microM), when photoexcited with UVB (280 to 360 nm) radiation, caused about 80% release of [3H]serotonin. No degranulation occurred with 20 microM benoxaprofen and UVB doses up to 7.2 kJ/m2. Trypan blue staining correlated well with degranulation caused by acridine plus UVA; however, with pyrene plus UVB there was greater [3H]serotonin release than dye uptake. Excitation of photosensitizers with doses of UV radiation that did not cause trypan blue staining suppressed degranulation of mast cells in response to chemical stimulation. Acridine, pyrene, and benoxaprofen in the presence of UV radiation inhibited the mast cells from responding to compound 48/80 or the calcium ionophore, chlortetracycline. Two other phototoxic compounds, chlorpromazine and deoxytetracycline, also abolished degranulation by compound 48/80. These findings indicate that phototoxic compounds: (1) cause degranulation in the presence of high doses of UV radiation; and (2) suppress degranulation of mast cells in response to secretory stimuli at doses of UV radiation that do not cause release of mediator.
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D003033:Coal Tar / Q000633:toxicity*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D010787:Photosensitivity Disorders / Q000139:chemically induced*; D011422:Propionates / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D014466:Ultraviolet Rays
D011422:Propionates; C011677:benoxaprofen; D012701:Serotonin; D003033:Coal Tar