Free radicals upregulate complement expression in rabbit isolated heart

Autor: Ruth A. Washington, Elaine J. Tanhehco, Koji Yasojima, Benedict R. Lucchesi, Patrick L. McGeer
Rok vydání: 2000
Předmět:
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 279:H195-H201
ISSN: 1522-1539
0363-6135
DOI: 10.1152/ajpheart.2000.279.1.h195
Popis: 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 μM) 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 μM), 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.
Databáze: OpenAIRE