Paradoxical rise of hemolytic complement in the blood of mice during zymosan- and liposome-induced CARPA: A pilot study

Abstract

The complement (C) activating effect of zymosan and liposomal drugs (AmBisome, Caelyx) leads to significant C consumption in rats, dogs, pigs and other species in vivo, as reflected by a fall in hemolytic complement activity (HCA) of their plasma. However, the acute C activating effect of zymosan and liposomal drugs is unclear in the mouse. Therefore, using sheep red blood cells, we assayed the HCA of plasma obtained from apolipoprotein E-deficient (ApoE) as well as from background C57BL/6 (BL6) mice. Intravenous (i.v.) administration of C activators led to a significant rise (up to 40%) in HCA of the plasma. The HCA steadily rose up to 30 min in ApoE mice, while it peaked at 3 min in BL6 mice, returning to baseline thereafter. The elevated HCA after IV injection of C activators is "paradoxical" in mice, since it implies an increase rather than a decrease in C levels in the blood. One possible explanation of the phenomenon is hemoconcentration due to anaphylatoxin-induced capillary leakage, resulting in an apparent rise of HCA. In conclusion, these preliminary observations highlight, for the first time, a species-dependent opposing impact of C activation and the resulting anaphylatoxin actions on hemolytic complement activity.