Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases.
We recently showed that culture-derived metacyclic trypomastigotes (CMT), but not epimastigotes (Epi), of the Miranda 88 strain of Trypanosoma cruzi evade lysis by the human alternative complement pathway because of inefficient binding of factor B to complement component C3b on the parasite surface. These results suggested that CMT and tissue-culture-derived trypomastigotes (TCT), which also activate the alternative pathway poorly, might produce a molecule capable of interfering with factor B binding to C3b. We now demonstrate that CMT and TCT lysates, as well as molecules spontaneously shed from CMT and TCT but not Epi, accelerate decay of 125I-labeled factor Bb from the alternative-pathway C3 convertase (C3bBb) assembled on zymosan or Epi and also accelerate decay of the classical-pathway C3 convertase (C4b2a) on sheep erythrocytes. Parasites metabolically labeled with [35S]methionine spontaneously shed a limited number of radioactive components ranging in molecular mass from 86 to 155 kDa for trypomastigotes and 25 to 80 kDa for Epi. Decay-accelerating activity within supernatants is inactivated by papain and is coeluted with 35S-containing polypeptides on FPLC anion-exchange chromatography, suggesting that the active constituents are protein molecules. Molecules with decay-accelerating activity may explain the developmentally regulated resistance to complement-mediated lysis in infective and vertebrate stages of the T. cruzi life cycle.
Rimoldi
M T
MT
Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Sher
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A
Heiny
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Lituchy
A
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Hammer
C H
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Joiner
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D000818:Animals; D003166:Complement Activating Enzymes / Q000378:metabolism*; D050577:Complement C3-C5 Convertases / Q000378:metabolism*; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000302:isolation & purification; D006790:Host-Parasite Interactions; D006801:Humans; D007700:Kinetics; D014349:Trypanosoma cruzi / Q000254:growth & development* / Q000502:physiology
D003165:Complement System Proteins; D003166:Complement Activating Enzymes; D050577:Complement C3-C5 Convertases