Endothelial cell signalling induced by trans-sialidase from Trypanosoma cruzi.
The protozoan responsible for Chagas' disease, Trypanosoma cruzi, expresses on its surface an unusual trans-sialidase enzyme thought to play an important role in host-parasite interactions. Trans-sialidase is the product of a multigene family encoding both active and inactive proteins. We have demonstrated that despite lacking enzymatic activity due to a single mutation, Tyr342-His, inactive trans-sialidase displays sialic acid binding activity, with identical specificity to that of its active analogue. In this work we demonstrate that binding of a recombinant inactive trans-sialidase to molecules containing alpha2,3-linked sialic acid on endothelial cell surface triggers NF-kappaB activation, expression of adhesion molecules and upregulation of parasite entry into host cells. Furthermore, inactive recombinant trans-sialidase blocks endothelial cell apoptosis induced by growth factor deprivation. These results suggest that inactive members of the trans-sialidase family play a role in endothelial cell responses to T. cruzi infection.
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, 22944.970, Rio de Janeiro, RJ, Brazil.
Wagner B
WB
Dias
Fernanda D
FD
Fajardo
Aurelio V
AV
Graça-Souza
Leonardo
L
Freire-de-Lima
Fabiana
F
Vieira
Murielle F
MF
Girard
Bernard
B
Bouteille
José O
JO
Previato
Lucia
L
Mendonça-Previato
Adriane R
AR
Todeschini
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002460:Cell Line; D042783:Endothelial Cells / Q000469:parasitology*; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020125:Mutation, Missense; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017354:Point Mutation; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*
D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D050505:Mutant Proteins; D016328:NF-kappa B; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C069715:trans-sialidase; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid