Free radicals upregulate complement expression in rabbit isolated heart

Both free radicals and complement activation can injure tissue. Our study d etermined whether free radicals alter complement production by the myocardi um. Isolated hearts from New Zealand White rabbits were perfused on a Lange ndorff apparatus and exposed to xanthine (X; 100 mu M) plus xanthine oxidas e (XO; 8 mU/ml) (X/XO). The free radical-generating system significantly (P < 0.05) increased C1q and also increased C1r, C3, C8, and C9 transcription compared with controls. Immunohistological examination revealed augmented m embrane attack complex deposition on X/XO-treated tissue. X/XO-treated hear ts also exhibited significant (P< 0.05) increases in coronary perfusion pre ssure and left ventricular end-diastolic pressure and a decrease in left-ve ntricular developed pressure. N-(2-mercaptopropionyl)- glycine (3 mM), in c onjunction with the superoxide dismutase mimetic SC-52608 (100 mu M), signi ficantly (P< 0.05) reduced the upregulation of C1q, C1r, C3, C8, and C9 mRN A expression elicited by X/XO. The antioxidants also ameliorated the deteri oration in function caused by X/XO. Local complement activation may represe nt a mechanism by which free radicals mediate tissue injury.