Effects of zinc chloride on guinea pig complement component activity in vitro: concentration-dependent inhibition and enhancement.
We have studied the in vitro effects of zinc chloride on the hemolytic activity of each component of the guinea pig classical complement pathway over a wide range (25 to 500 muM) of zinc concentrations. At high concentrations (>200 muM) the activity of all components was strongly inhibited by this metal. Concentrations of 500 muM inhibited C1 and C5 by 80 and 65%, respectively, whereas all other components were inhibited by more than 94%. Zinc chloride at 25 muM produced more varied effects, with C2, C3, and C6 inhibited by 36, 35, and 55%. C7 and C8 were inhibited by approximately 25%, whereas C1, C4, and C9 were not appreciably affected. The activity of the fifth component, on the other hand, was strongly enhanced by the presence of zinc. Concentrations of 25, 50, and 100 muM zinc chloride produced increases of 92, 44, and 18%, respectively, in C5 titers when present during the activation-binding step of this component. Further studies indicated that the activities of cell-bound complement components were unaffected by zinc treatment after activation and/or binding to the sheep erythrocyte surface had occurred. In addition, zinc did not appear to inhibit by causing irreversible denaturation of either total complement proteins or its various components. Rather, it appears that zinc must be present as a reactant during the activation and/or binding step of each component for inhibition or enhancement to occur.
D000818:Animals; D003167:Complement Activation / Q000187:drug effects*; D003172:Complement C1 / Q000276:immunology; D003175:Complement C2 / Q000276:immunology; D003176:Complement C3 / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D003182:Complement C5 / Q000276:immunology; D003183:Complement C6 / Q000276:immunology; D003171:Complement Pathway, Classical / Q000187:drug effects*; D003165:Complement System Proteins / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D015032:Zinc / Q000494:pharmacology*
D003172:Complement C1; D003175:Complement C2; D003176:Complement C3; D003181:Complement C4; D003182:Complement C5; D003183:Complement C6; D003165:Complement System Proteins; D015032:Zinc