The trans-sialidase from Trypanosoma cruzi triggers apoptosis by target cell sialylation.
The trans-sialidase, a modified sialidase that transfers sialyl residues among macromolecules, is a unique enzymatic activity expressed by some parasitic trypanosomes being essential for their survival in the mammalian host and/or in the insect vector. The enzyme from Trypanosoma cruzi, the agent of Chagas disease, is found in blood and able to act far from the infection site by inducing apoptosis in cells from the immune system. A central and still unsolved question is whether trans-sialidase-mediated addition or removal of sialic acid to/from host acceptor molecules is the event associated with the apoptosis induced by the enzyme. Here we show that lactitol, a competitive inhibitor that precluded the transference of the sialyl residue to endogenous acceptors but not the hydrolase activity of the enzyme, prevented ex vivo and in vivo the apoptosis caused by the trans-sialidase. By lectin histochemistry, the transference of sialyl residue to the cell surface was demonstrated in vivo and found associated with the apoptosis induction. The sialylation of the CD43 mucin, a key molecule involved in trans-sialidase-apoptotic process, was readily detected and also prevented by lactitol on thymocytes. Therefore, lesions induced by trans-sialidase on the immune system are due to the sialylation of endogenous acceptor molecules.
Mucci
Juan
J
Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, Consejo Nacional de Investigaciones Científicas y Técnicas and Universidad Nacional de San Martín, Buenos Aires, Argentina.
Risso
Marikena G
MG
Leguizamón
M Susana
MS
Frasch
Alberto C C
AC
Campetella
Oscar
O
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013402:Sugar Alcohols / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D046509:Tissue Culture Techniques; D014349:Trypanosoma cruzi / Q000201:enzymology / Q000472:pathogenicity*
D006023:Glycoproteins; D013402:Sugar Alcohols; C069715:trans-sialidase; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; C014635:lactitol