APOPTOSIS INDUCTION IN THE IMMUNE SYSTEM BY ALTERED SIALYLATION PATTERNS.

TRIBULATTI MV, MUCCI J, LEGUIZAMON MS AND CAMPETELLA O.

Angra Dos Reis, Brasil

Simposio; 6th International Cell Death Symposium on "The Mechanisms of Cell Death in Cancer and Aging"; 2006

Sialylation is among the most important modifications of the cell surface glycoconjugates. It leads to the acquisition /loss of a negative charge and to the ability to interact with several lectins and receptors then being involved in signaling several biologic processes such us extravasation, homing, etc. Its modification might induce strong physiologic alterations. Trypanosoma cruzi, the agent of Chagas disease, sheds an enzyme known as trans-sialidase (TS) that is able to mediate the transference of sialyl residues among macromolecules. We found that TS mediates the apoptosis-induced cell depletion in organs of the immune system mimicking findings in infected animals. Damage observed during infection can be prevented by the passive transfer of TS-neutralizing antibodies. The TS-mediated transfer of sialyl residues to acceptor cells induces aberrant sialylation patterns that are recognized leading to their apoptosis. Inhibition of sialylation but not sialic acid hydrolysis by lactitol addition prevents apoptosis. In the thymus, TS-induction of cell death requires the presence of a) androgens since no effect was observed in female and in flutamide-treated or castrated male mice b) CD43 and c) TNFa since KO mice resists TS treatment. Therefore, TS provides a tool to understand the relevance of the sialylation in the regulation of cell responses by apoptosis induction. J Infect Dis 180:1398, 1999; PNAS 99:3896, 2002; J Immunol 174:4545, 2005; Cell Microbiol in press.