Free radicals upregulate complement expression in rabbit isolated heart.
Both free radicals and complement activation can injure tissue. Our study determined whether free radicals alter complement production by the myocardium. Isolated hearts from New Zealand White rabbits were perfused on a Langendorff apparatus and exposed to xanthine (X; 100 microM) plus xanthine oxidase (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 membrane attack complex deposition on X/XO-treated tissue. X/XO-treated hearts also exhibited significant (P < 0.05) increases in coronary perfusion pressure and left ventricular end-diastolic pressure and a decrease in left-ventricular developed pressure. N-(2-mercaptopropionyl)-glycine (3 mM), in conjunction with the superoxide dismutase mimetic SC-52608 (100 microM), significantly (P < 0.05) reduced the upregulation of C1q, C1r, C3, C8, and C9 mRNA expression elicited by X/XO. The antioxidants also ameliorated the deterioration in function caused by X/XO. Local complement activation may represent a mechanism by which free radicals mediate tissue injury.
Tanhehco
E J
EJ
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Yasojima
K
K
McGeer
P L
PL
Washington
R A
RA
Lucchesi
B R
BR
D000818:Animals; D015922:Complement C1q / Q000235:genetics; D003176:Complement C3 / Q000235:genetics; D003185:Complement C8 / Q000235:genetics; D003186:Complement C9 / Q000235:genetics; D003165:Complement System Proteins / Q000235:genetics*; D005609:Free Radicals / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D011951:Receptors, Complement / Q000235:genetics; D014158:Transcription, Genetic; D019820:Xanthine / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D003176:Complement C3; D003185:Complement C8; D003186:Complement C9; D005609:Free Radicals; D011951:Receptors, Complement; D019820:Xanthine; D015922:Complement C1q; D003165:Complement System Proteins; D014969:Xanthine Oxidase