A T. cruzi-secreted protein immunologically related to the complement component C9: evidence for membrane pore-forming activity at low pH.
Protozoan parasite T. cruzi invades cells within acidic vacuoles, but shortly afterward escapes into the cytosol. Exit from the phagosome is blocked by raising the pH of acidic compartments, suggesting that a previously described acid-active hemolysin secreted by T. cruzi might be involved in the membrane disruption process. Here we show that T. cruzi supernatants are cytotoxic for nucleated cells at pH 5.5 and contain a protein reactive with antibodies against reduced and alkylated human C9 (the ninth component of complement). The C9 cross-reactive protein (TC-TOX) copurified with the cytolytic activity, and the active fractions induced conductance steps characteristic of transmembrane ion channels in planar phospholipid bilayers. Immunocytochemical studies using antibodies against purified TC-TOX showed that the protein was localized to the luminal space of parasite-containing phagosomes. We postulate that TC-TOX, when secreted into the acidic environment of the phagosome, forms pores in the membrane, which contribute to its disruption.
Andrews
N W
NW
Department of Pathology, Kaplan Cancer Center, New York University Medical Center, New York 10016.
Abrams
C K
CK
Slatin
S L
SL
Griffiths
G
G
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003186:Complement C9 / Q000276:immunology; D003429:Cross Reactions; D004553:Electric Conductivity; D006168:Guinea Pigs; D006461:Hemolysis; D006863:Hydrogen-Ion Concentration; D015151:Immunoblotting; D008051:Lipid Bilayers; D008854:Microscopy, Electron; D015800:Protozoan Proteins; D013347:Subcellular Fractions / Q000648:ultrastructure; D014349:Trypanosoma cruzi / Q000502:physiology* / Q000648:ultrastructure
D003186:Complement C9; D008051:Lipid Bilayers; D015800:Protozoan Proteins