High-density-lipoprotein-independent killing of Trypanosoma brucei by human serum.
The cattle pathogen Trypanosoma brucei brucei is morphologically indistinguishable from the human pathogens T.b. rhodesiense and T.b. gambiense. However, unlike the human pathogens, T.b. brucei is lysed by normal human serum (NHS). The trypanolytic factor in NHS co-purifies with high-density lipoproteins (HDL), but its precise nature is unknown. Using a new fluorescence-based viability assay to assess T.b. brucei killing, we find that the HDL-deficient sera from two patients with Tangier disease are as trypanolytic as NHS. Fractionation of the Tangier sera by density ultracentrifugation revealed that the activity resides only in lipoprotein-depleted fractions. Tangier and NHS were also subjected to molecular sieving chromatography, and the activity profiles were identical. Lytic fractions to T. brucei (but not to T. rhodesiense) appeared under two distinct peaks of 100-600 kDa and > 1000 kDa. Neither peak coincided with the position of the major serum lipoproteins, as determined by cholesterol titrations. The high-molecular-mass peak did not contain the HDL-associated apolipoprotein-A1. Further, we did not find that purified apolipoproteins A1 or J are lytic for the trypanosomes. We conclude that the killing of T. brucei by human serum can be independent of HDL.
Tomlinson
S
S
Michael Heidelberger Division of Immunology, New York University Medical Center, NY 10016, USA.
Jansen
A M
AM
Koudinov
A
A
Ghiso
J A
JA
Choi-Miura
N H
NH
Rifkin
M R
MR
Ohtaki
S
S
Nussenzweig
V
V
D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001685:Biological Factors / Q000302:isolation & purification* / Q000502:physiology; D001790:Blood Physiological Phenomena; D002499:Centrifugation, Density Gradient; D002850:Chromatography, Gel; D006801:Humans; D007113:Immunity, Innate; D008075:Lipoproteins, HDL; D008970:Molecular Weight; D013631:Tangier Disease / Q000097:blood; D014346:Trypanosoma brucei brucei
D016632:Apolipoprotein A-I; D001685:Biological Factors; D008075:Lipoproteins, HDL