DEVELOPMENTALLY-REGULATED SENSITIVITY OF TRYPANOSOMA-BRUCEI-BRUCEI TOTHE CYTOTOXIC EFFECTS OF HUMAN HIGH-DENSITY-LIPOPROTEIN

Citation
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
Citations number
34
Categorie Soggetti
Parasitiology
Journal title
ISSN journal
00144894
Volume
81
Issue
2
Year of publication
1995
Pages
216 - 226
Database
ISI
SICI code
0014-4894(1995)81:2<216:DSOTT>2.0.ZU;2-Y
Abstract
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.