Trypanolytic activity in vivo of plasma from patients with schistosomiasis against the African trypanosome,. Trypanasom h c e i h c e i. RUTH E. BUNDY, JAMES 3 ...
Biochemical Society Transactions (1 996) 24 439s
Trypanolytic activity in vivo of plasma from patients with schistosomiasis against the African trypanosome, Trypanasom h c e i h c e i RUTH E. BUNDY, JAMES 3. OWEN, VERA L.M. LIMA* and ELIZABETH M. C. CHAVES Medical Unit, Royal Free Hospital School of Medicine, London NW3 2PF, England and 'Departamento de Bioquimica, Centro de CiBncias Bioldgicas, Universidade Federalde Pernambuco, Recife-PE, 50.670-420, Brazil. The prevalence of three subspecies of the parasitic haemoflagellate,Trypanosoma brucei in equatorial Africa poses a severe constraint to improvement of human welfare. T. b. gambiense and T. b. rhodesiense are the infective agents of chronic and acute forms of human sleeping sickness, respectively, while T. b. brucei causes nagana in cattle and other domestic livestock thereby increasing nutritional and economic problems for the human population. Humans are naturally immune to T. b. brucei because their serum lyses this unicellular protozoan [ 11. Surprisingly, the means of protection is high-density lipoproteins (HDL), which the trypanosomes engulf through a physiological, receptor-mediatedpathway for delivery to acidic intracellular vesicles [2,3]. However, clear identification of the active particles, their essential cytotoxic constituents and detailed mode of action remains elusive [4-61. Dyslipoproteinaemia is a common feature of humans infected with the parasitic helminth, Schistosoma mansoni, many patients having low amounts of HDL with an abnormal lipid [7], and perhaps apolipoprotein [8], composition. In this study, we have assessed the trypanolytic activity in vivo of sera from normal subjects compared to that from patients with schistosomiasis and have correlated it with the concentrations of the main HDL components. Blood samples were obtained from 8 healthy volunteers and from 19 Brazilian patients with well-characterized S. mansoni [9], anticoagulated with EDTA and the plasma stored at -2O'C until use. The total cholesterol, apoA-l and apoA-ll contents of plasma HDL were measured after precipitation of the non-HDLlipoproteinswith phosphotungsticacid and MgCI,. Suspensions of human serum-sensitive, pleomorphic T. b. brucei (strain STlB 345AD [4,5]) were used to infect T/O mice as described previously [4,10]. The parasitaemia was allowed to reach -2.5 x 10 cells per ml blood, as judged by microsocopic examination of tail bleeds, and then each mouse was injected intraperitoneally with test plasma (0.5 ml). The survival times in days were recorded; control mice received saline and survived less than 1 day. Plasma levels of HDL-cholesterol were 32 % lower in the patients (32.0k2.7 mg/dl; meaniSEM) compared to normal subjects (46.9k5.3 mg/dl, P
