Mol Biochem Parasitol 2001 Oct;117(2):129-36
Activity of human trypanosome lytic factor in mice.
Barker C, Barbour KW, Berger FG, Hajduk SL.
Department of Biochemistry and Molecular Genetics, School of
Medicine,
University of Alabama at Birmingham, Birmingham, AL
35394, USA.
The inability of the cattle pathogen Trypanosoma brucei brucei to
infect
humans is due to an innate factor in human serum termed
Trypanosome Lytic Factor (TLF). Human haptoglobin-related protein is
the proposed toxin in TLF and can exist either as a
component of a minor subclass of high-density lipoprotein (TLF-1) or
as a lipid free, high molecular weight protein complex (TLF-2). The
trypanolytic
activity of both TLF-1 and TLF-2 has been studied in vitro but their
relative
contributions to protection against T. b. brucei infection in vivo has
not been established. In the present studies we show that treatment of
T. b. brucei infected mice with TLF-1 resulted in a dose dependent
decrease
in parasite numbers but did not affect parasite numbers in mice
infected
with Trypanosoma brucei rhodesiense, the causative agent of the human
sleeping
sickness. Similarly, pretreatment of mice with TLF-1 resulted in
protection
against a challenge by T. b. brucei but had no effect on T. b.
rhodesiense
challenge. Induction of the acute phase protein haptoglobin, a natural
antagonist of TLF-1, diminished but did not abolish the protection
against
trypanosome challenge. In addition, haptoglobin knockout mice showed
higher
levels of TLF-1 mediated protection against a T. b. brucei challenge.
These
results suggest that while TLF-1 is active in vivo, even in the
presence
of elevated levels of haptoglobin, its activity is modulated in a dose
dependent fashion by haptoglobin in the circulation.