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 (/sup 3/H)serotonin and (/sup 14/C)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 ,f 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.
- Research Organization:
- Univ. of California, San Diego
- OSTI ID:
- 6589154
- Journal Information:
- J. Invest. Dermatol.; (United States), Vol. 3
- Country of Publication:
- United States
- Language:
- English
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MAST CELLS
BIOLOGICAL RADIATION EFFECTS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PORPHYRINS
RADIOSENSITIVITY EFFECTS
PROTOPORPHYRINS
ARACHIDONIC ACID
CALCIUM
CARBON 14 COMPOUNDS
CELL MEMBRANES
MICE
OXYGEN
SEROTONIN
SKIN DISEASES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALINE EARTH METALS
AMINES
ANIMAL CELLS
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZAARENES
AZOLES
CARBOXYLIC ACIDS
CARCINOGENS
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DISEASES
DRUGS
ELEMENTS
ESTERS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MEMBRANES
METALS
MONOCARBOXYLIC ACIDS
NEUROREGULATORS
NONMETALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIGMENTS
PYRROLES
RADIATION EFFECTS
RADIOPROTECTIVE SUBSTANCES
RODENTS
SOMATIC CELLS
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture
560300 - Chemicals Metabolism & Toxicology