The effect of 8-methoxypsoralen plus long-wave ultraviolet (PUVA) radiation on mast cells: PUVA suppresses degranulation of mouse skin mast cells induced by compound 48/80 or concanavalin A.
In order to see whether 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet (UVA) radiation (PUVA) has an influence on immediate-type skin reactions, we have undertaken an animal study. Ears of mice were treated with a 0.5% 8-MOP solution topically plus UVA radiation (1.5-2.5 J/cm2). After PUVA radiation, skin responses to intradermal injection with mast cell liberators, including compound 48/80 (2.5 mg/ml, 10 microliter) and concanavalin A (Con-A) (2.0 mg/ml), or with a mixture of 5-hydroxytryptamine (5-HT) and histamine as vasodilator (1.0 mg/ml and 50 mM, respectively) were examined with time (2 h-14 days). At each time point, an ear swelling response (ESR) was measured with a dial thickness gauge. The rate of mast cell degranulation and mast cell numbers were assessed by light microscopy using toluidine blue-stained semithin (1 micron) sections. ESR induced by compound 48/80 or Con-A was significantly suppressed dose-dependently (greater than 42% inhibition) by PUVA between 2 h-3 days postirradiation as compared with that in nonirradiated control mice, and the value returned to normal levels by 7-14 days. Compound 48/80- or Con-A-induced mast cell degranulation (%) was remarkably decreased between 2 h-3 days (greater than 48% inhibition) in accordance with the suppression in ESR and it was restored to the rates in nonirradiated controls by 7-14 days. Neither ESR nor percent degranulation was affected by UVA radiation only (less than 3.5 J/cm2) or application of 8-MOP only. 5-HT plus histamine-mediated ESR was not altered at all by PUVA throughout the experimental period. Since PUVA radiation itself at given doses did not produce measurable ESR, mast cell degranulation, or a reduction in mast cell numbers, and since PUVA did not affect a normal vascular response to vasodilator, it seemed that decreased skin reactivity to mast cell degranulators by PUVA might be due to a PUVA-induced noncytolytic alteration in mast cell release mechanisms.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D003208:Concanavalin A / Q000494:pharmacology*; D000078404:Epidermal Cells; D005260:Female; D006632:Histamine / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D011701:PUVA Therapy; D010778:Photochemotherapy; D013997:Time Factors; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D003208:Concanavalin A; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D006916:5-Hydroxytryptophan