Role of phospholipids in the cytotoxic action of high density lipoprotein on trypanosomes.
Host range among the African trypanosomes, protozoa that cause fatal diseases both in humans and livestock, may be, in part, regulated by toxic properties associated with host high density lipoproteins (HDL). High density lipoproteins from hosts resistant (baboon, human) or susceptible (rabbit, rat) to Trypanosoma brucei infection were isolated and their trypanocidal activity was determined in in vitro cell lysis assays. Rabbit and rat HDL were not cytotoxic while baboon and human HDL rapidly lysed trypanosomes within 2 h at 37 degrees C. Analysis of the phospholipid composition of HDL preparations from these species suggested a correlation between trypanocidal activity and low phosphatidylinositol content. Phospholipase digestion of HDL resulted in a loss of trypanocidal activity, indicating the importance of native phospholipids in maintaining this biological activity of HDL. Cell lysis and loss of trypanosome infectivity induced by baboon HDL could be inhibited either by addition of rabbit or rat HDL to the incubation medium or by addition of purified phospholipids, phosphatidylinositol being the most effective inhibitor. Although the mechanism by which HDL lyses trypanosomes remains to be elucidated, these results suggest an important role for phospholipids in determining the specificity of this cytotoxic property of HDL.
Rifkin
M R
MR
Rockefeller University, New York 10021.
D000818:Animals; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010215:Papio; D010713:Phosphatidylcholines / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000494:pharmacology; D010740:Phospholipases / Q000494:pharmacology; D010743:Phospholipids / Q000502:physiology* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D014344:Trypanocidal Agents / Q000097:blood / Q000633:toxicity*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000378:metabolism
D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D010743:Phospholipids; D014344:Trypanocidal Agents; D010740:Phospholipases