Photodynamic action of uroporphyrin on the complement system in porphyria cutanea tarda.
We investigated the effect of UV light (320-460 nm) on total hemolytic CH50 activity and C3 cleavage in sera obtained from 14 patients with porphyria cutanea tarda. Irradiation with 5, 10, or 50 J/cm2 resulted in a 12%-60% loss of CH50 and a 5%-30% cleavage of native C3 as estimated by planimetric evaluation of the immunoelectrophoretic C3 pattern. The complement changes were most pronounced in sera from patients with active disease and were minimal or absent in patients who were in remission. In all cases, the decrease of CH50 and C3 cleavage was proportional to the plasma-porphyrin concentration and the dose of radiation. After exposure to 320- to 460-nm light, similar changes were seen in normal human serum (NHS) to which exogenous uroporphyrin had been added. Beta-carotene and chloroquine had no inhibitory effect on the photodynamic complement activation. The C3 cleavage in irradiated NHS containing uroporphyrin was not affected by 10 mM EGTA, but was partially inhibited in the presence of 30 mM EDTA, thus indicating that the interaction of photoexcited uroporphyrin with the complement system differs from classical-pathway complement activation.
D000368:Aged; D002338:Carotenoids / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000528:radiation effects; D003165:Complement System Proteins / Q000528:radiation effects*; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D008297:Male; D008875:Middle Aged; D011164:Porphyrias / Q000097:blood*; D011166:Porphyrins / Q000494:pharmacology*; D012871:Skin Diseases / Q000097:blood*; D014466:Ultraviolet Rays; D014578:Uroporphyrins / Q000494:pharmacology*; D019207:beta Carotene
D003176:Complement C3; D011166:Porphyrins; D014578:Uroporphyrins; D019207:beta Carotene; D002338:Carotenoids; D004533:Egtazic Acid; D002738:Chloroquine; D003165:Complement System Proteins; D004492:Edetic Acid