title: Characterization of primate trypanosome lytic factors.
abstract: Humans are one of the few species that resist infection by Trypanosoma brucei brucei because the parasites are killed by lytic factors found in human serum. Trypanosome lytic factors (TLFs) are protein/lipid complexes that contain apolipoprotein A-I (apoA-I), and are therefore a class of high density lipoproteins (HDLs). Haptoglobin-related protein (Hpr) is a unique protein component of TLFs, and its expression has only been demonstrated in humans. Trypanolytic activity has only been found in the sera of five primates: humans, gorillas, mandrills, baboons and sooty mangabeys. We describe here previously unidentified components of highly purified human TLF1: apolipoprotein L-I (apoL-I), human cathelicidin antimicrobial peptide 18 (hCAP18) and glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD). However, we found that hCAP18 and GPI-PLD, along with apoA-I, are common components of both lytic and non-lytic primate HDLs. In contrast, Hpr, which has been previously implicated as the main lytic component of TLF1, was a unique component of all trypanolytic primate HDLs. Furthermore, a polyclonal antiserum to Hpr neutralized the lytic activity from humans and baboons. ApoL-I, a candidate lytic component of human serum, was not immunologically or genetically detectable in two primate species with lytic activity. Polyclonal antiserum to apoL-I also did not neutralize TLF activity in a total human HDL preparation. These findings suggest that apoL-I is not essential in all primate TLFs, and apoL-I alone is not sufficient for optimal trypanosome lytic activity in human TLF.
authors.affiliation: Department of Medical and Molecular Parasitology, New York University School of Medicine, 341, East 25th Street, New York, NY 10010, USA.
authors.forename: Elena B
authors.initials: EB
authors.lastname: Lugli
authors.forename: Michael
authors.initials: M
authors.lastname: Pouliot
authors.forename: Maria Del Pilar Molina
authors.initials: Mdel P
authors.lastname: Portela
authors.forename: Michael R
authors.initials: MR
authors.lastname: Loomis
authors.forename: Jayne
authors.initials: J
authors.lastname: Raper
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000097:blood / Q000737:chemistry / Q000235:genetics; D023181:Antimicrobial Cationic Peptides / Q000032:analysis* / Q000737:chemistry; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000032:analysis* / Q000737:chemistry; D001798:Blood Proteins / Q000737:chemistry / Q000235:genetics; D000882:Haplorhini; D006242:Haptoglobins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008075:Lipoproteins, HDL / Q000032:analysis* / Q000097:blood / Q000737:chemistry*; D008969:Molecular Sequence Data; D010739:Phospholipase D / Q000032:analysis* / Q000737:chemistry; D011323:Primates; D017422:Sequence Analysis, DNA; D014346:Trypanosoma brucei brucei / Q000276:immunology*; D054804:Cathelicidins
chemical_list: C108666:APOL1 protein, human; D000951:Antigens, Neoplasm; D023181:Antimicrobial Cationic Peptides; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D001798:Blood Proteins; C058632:HPR protein, human; D006242:Haptoglobins; D008075:Lipoproteins, HDL; C434063:TLF1 protein, human; D010739:Phospholipase D; C065017:glycoprotein phospholipase D; D054804:Cathelicidins