Ca2+ is essential cofactor for trypanocidal activity of normal human serum

Normal human serum has been known to exert a cytotoxic effect on Trypanosoma brucei subspecies for nearly 80 yr. But in spite of many attempts, no trypanocidal factor was found in human or baboon serum, until Rifkin demostrated a high density lipoprotein (HDL) in normal human serum with trypanocidal activity. The conclusion that this was the trypanocidal factor was supported by the report that serum from patients with Tangier disease, characterised by a severe deficiency of HDL, lacked trypanocidal activity. We report here that Ca2+ is an essential cofactor for the trypanocidal activity of normal human serum, in which alpha2 macroglobulin (alpha 2) might function as a Ca2+-carrier. We further show that D-glucose, D-fructose and D-mannose can suppress the trypanocidal action of normal human serum, whereas glycerol has the opposite effect.