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.
Dias
Wagner B
WB
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Ilha do Fundão, 22944.970, Rio de Janeiro, RJ, Brazil.
Fajardo
Fernanda D
FD
Graça-Souza
Aurelio V
AV
Freire-de-Lima
Leonardo
L
Vieira
Fabiana
F
Girard
Murielle F
MF
Bouteille
Bernard
B
Previato
José O
JO
Mendonça-Previato
Lucia
L
Todeschini
Adriane R
AR
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