Amastigotes of Trypanosoma cruzi escape destruction by the terminal complement components.
We studied the effect of complement on two life cycle stages of the protozoan parasite Trypanosoma cruzi: epimastigotes, found in the insect vector, and amastigotes, found in the mammalian host. We found that while both stages activate vigorously the alternative pathway, only epimastigotes are destroyed. The amounts of C3 and C5b-7 deposited on the amastigotes were similar to those bound to the much larger epimastigotes. Binding of C9 to amastigotes was four to six times less than binding to epimastigotes, resulting in a lower C9/C5b-7 ratio. Although a fairly large amount of C9 bound stably to amastigotes, no functional channels were formed as measured by release of incorporated 86Rb. The bound C9 had the characteristic properties of poly-C9, that is, it expressed a neo-antigen unique to poly-C9, and migrated in SDS-PAGE with an apparent Mr greater than 10(5). The poly-C9 was removed from the surface of amastigotes by treatment with trypsin, indicating that it was not inserted in the lipid bilayer. Modification of amastigote surface by pronase treatment rendered the parasites susceptible to complement attack. These results suggest that amastigotes have a surface protein that binds to the C5b-9 complex and inhibits membrane insertion, thus protecting the parasites from complement-mediated lysis.
Iida
K
K
Department of Pathology, New York University Medical Center, New York 10016.
Whitlow
M B
MB
Nussenzweig
V
V
D000818:Animals; D014355:Chagas Disease / Q000276:immunology; D003167:Complement Activation; D003176:Complement C3 / Q000276:immunology; D003182:Complement C5 / Q000276:immunology; D050776:Complement C5b; D003184:Complement C7 / Q000276:immunology; D003186:Complement C9 / Q000276:immunology; D003170:Complement Pathway, Alternative; D003165:Complement System Proteins / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008051:Lipid Bilayers / Q000276:immunology; D011402:Pronase / Q000494:pharmacology; D012414:Rubidium Radioisotopes; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D014357:Trypsin / Q000494:pharmacology
D003176:Complement C3; D003182:Complement C5; D003184:Complement C7; D003186:Complement C9; D008051:Lipid Bilayers; D012414:Rubidium Radioisotopes; D050776:Complement C5b; D003165:Complement System Proteins; D014357:Trypsin; D011402:Pronase