Dr. Moore et al., DEVELOPMENTALLY-REGULATED SENSITIVITY OF TRYPANOSOMA-BRUCEI-BRUCEI TOTHE CYTOTOXIC EFFECTS OF HUMAN HIGH-DENSITY-LIPOPROTEIN, Experimental parasitology, 81(2), 1995, pp. 216-226
The bloodstream developmental stages of the protozoan parasite Trypano
soma brucei brucei are lysed by normal human serum. The cytotoxic fact
or is a minor sub-class of human high-density lipoprotein termed trypa
nosome lyric factor (TLF). T. b. brucei rapidly develops resistance to
TLF when incubated at 26 degrees C under conditions which allow diffe
rentiation to the procyclic, insect midgut developmental stage. This i
n vitro differentiation system allowed us to correlate loss of TLF sen
sitivity with other parameters of differentiation to the procyclic for
m. The onset of resistance to TLF occurs within 2 hr after shifting bl
oodstream forms to differentiation conditions. TLF resistance is corre
lated with a rapid but transient decrease in protein synthesis by the
parasite, is acquired prior to cell division at 26 degrees C, and prec
edes the loss of variant surface glycoprotein. Tn addition, we found b
inding and uptake of TLF by established procyclic trypanosomes was red
uced approximately fivefold relative to bloodstream trypanosomes and t
he TLF binding observed in procyclics was nonspecific. No TLF was boun
d to the procyclic flagellar pocket membrane and the procyclics failed
to endocytose any of the surface-bound TLF. In contrast, bloodstream
forms bind TLF via a flagellar pocket-localized protein and bound TLF
is taken up;by endocytosis. These findings suggest that resistance of
procyclic T. b. brucei to TLF-mediated lysis is due to a reduction in
the endocytosis of TLF by this developmental stage of the parasite. (C
) 1995 Academic Press, Inc.