In a recent paper, a linkage between immunological adjuvant activity in mice and in vitro anticomplementary (alternative pathway assay) effects was described for different polyanions. This connection was found only if mouse serum was used as a complement (C) source. In order to investigate the possible role of C in adjuvant activity, the differential effects of polyanions on mouse C were studied in detail. For this study, substances with different activity were selected, namely dextran sulphate with strong C-regulatory and immunoadjuvant activities, and heparin, which was weakly anticomplementary and devoid of adjuvant effect. In general, studies of mouse C are complicated by the inavailability of isolation procedures for the C-components involved. This difficulty was circumvented by making use of C5-deficient serum and of the haemolytic activity of mouse membrane attack complexes formed in the fluid phase. With yeast cells as alternative pathway activators it was shown that the effect of heparin on this pathway was restricted to activation of the terminal route. In contrast, dextran sulphate also caused a functional decay of a yeast-bound alternative pathway C5-convertase and interfered with the haemolytic activity of fluid-phase membrane attack complexes as well. Further studies will be needed to decide whether these specific effects of dextran sulphate are related to the immunological adjuvant activity of the substance in mice.
Alternative complement pathway activity in mouse peritoneal fluid was determined by a sensitive microtiter assay with rabbit erythrocytes as target cells and cobra venom factor as the inducer of bystander hemolysis. The intra-and interstrain variations in five mouse strains were 30% and, maximally, 64%, respectively. No activity was detected in genetically C5-deficient mice. In C5-sufficient mice, intraperitoneal injection of heat-inactivated Listeria monocytogenes resulted in a 250% increase in local complement activity within 30 min. This effect was reversed by simultaneous injection of dextran sulfate but not heparin. These results are discussed in relation to the ability of listeriae to activate the mouse alternative complement pathway in vitro and the effectiveness of dextran sulfate and the failure of heparin in functioning as an adjuvant in the induction of a protective response in mice by a heat-inactivated listeria vaccine.
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