Differential effects of protoporphyrin and uroporphyrin on murine mast cells.
To investigate the mechanisms responsible for the distinct cutaneous manifestations of erythropoietic protoporphyria and porphyria cutanea tarda, the effects of protoporphyrin (PP) and uroporphyrin (URO), the predominant porphyrins in the respective disease, on mast cells were examined. Release of preformed and generated mediators was assessed by the release of radioactivity from cells labeled with [3H]serotonin and [14C]arachidonic acid, respectively. Clinically relevant doses of PP (25-500 ng/ml) and 396-407 nm irradiation (3-16 X 10(2)J/m2) induced maximal net release of preformed mediators of 44.52 +/- 6.6 to 58.01 +/- 4.0% (mean +/- SE). In contrast, irradiation in the presence of URO (50-5000 ng/ml) resulted in less than 5% net release. [3H]Serotonin release induced by PP and irradiation was calcium-independent, and was not enhanced by phorbol 12-myristate 13-acetate, a known activator of protein kinase C. This release was suppressed by catalase, a scavenger of hydrogen peroxide. Furthermore, irradiation in the presence of PP, but not in the presence of URO, resulted in perturbation of cell membrane. Irradiation in the presence of PP also resulted in a maximal net release of generated mediators of 9.98 +/- 3.5% (mean +/- SE), whereas similar treatment in the presence of URO induced less than 0.5% net release. These results suggested that the burning, stinging, erythema, and edema experienced by patients with erythropoietic protoporphyria following sun exposure, and the lack of such findings in patients with porphyria cutanea tarda, may be explained, at least in part, by the differential effects of PP and URO on mast cells.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D001696:Biomechanical Phenomena; D002118:Calcium / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002462:Cell Membrane / Q000187:drug effects / Q000528:radiation effects; D005609:Free Radicals; D008407:Mast Cells / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology*; D011524:Protoporphyrins / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate; D014578:Uroporphyrins / Q000494:pharmacology*; D014965:X-Rays
D001095:Arachidonic Acids; D002250:Carbon Radioisotopes; D005609:Free Radicals; D011166:Porphyrins; D011524:Protoporphyrins; D014578:Uroporphyrins; D016718:Arachidonic Acid; D012701:Serotonin; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen; D002118:Calcium