Analytic study of the differential anticomplementary effects of dextran sulphate and heparin in the assay for the mouse alternative pathway.
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 unavailability 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.
J P
JP
Klerx
H
H
Van Dijk
W J
WJ
Van der Maaden
J M
JM
Willers
D000818:Animals; D003166:Complement Activating Enzymes / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects*; D003182:Complement C5; D003169:Complement Inactivator Proteins; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D003911:Dextrans / Q000494:pharmacology*; D005260:Female; D006461:Hemolysis; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D008722:Methods; D051379:Mice; D008811:Mice, Inbred DBA
D003182:Complement C5; D003169:Complement Inactivator Proteins; D003911:Dextrans; D006493:Heparin; D003166:Complement Activating Enzymes