Effect of some hydroxycoumarins on complement-mediated hemolysis in human serum.
Coumarin derivatives are known to possess antiinflammatory and antimetastatic properties due to their direct action on cells, predominantly on macrophages. In the present study the interactions between esculin, esculetin, fraxin, fraxetin, as well as their acetylated and methylated derivatives and non-cell system participating in inflammatory processes, comprised of serum complement proteins, were investigated in vitro. 7-Methylesculin, esculin 5Ac and esculetin 2Ac exhibited good inhibition on classical pathway (CP) activity and scoparone strongly reduced alternative pathway (AP) activity in normal human serum (NHS). Some of the hydroxycoumarins were able to enhance hemolysis. Seven derivatives were tested in C1 and C3 functional assays, as 7-methylesculin appeared to be the strongest inhibitor of both activities. Esculin (En) and scopoletin (St) altered the effect of other complement activators (heat aggregated IgG, suramin, and zymosan) when applied with them simultaneously in vitro.
Ivanovska
N
N
Department of Immunology, Bulgarian Academy of Sciences, Sofia.
Yossifova
T
T
Vassileva
E
E
Kostova
I
I
D002021:Buffers; D003172:Complement C1 / Q000502:physiology; D003176:Complement C3 / Q000502:physiology; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003171:Complement Pathway, Classical / Q000187:drug effects; D003165:Complement System Proteins / Q000502:physiology*; D003374:Coumarins / Q000494:pharmacology*; D004929:Esculin / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D012603:Scopoletin / Q000494:pharmacology
D002021:Buffers; D003172:Complement C1; D003176:Complement C3; D003169:Complement Inactivator Proteins; D003374:Coumarins; D004929:Esculin; D003165:Complement System Proteins; D012603:Scopoletin