IRIBARREN PABLO
Congresos y reuniones científicas
Título:
Peptidoglycan of staphylococcus aureus induces atypical cell death of microglial cells by a caspase-3 independent pathway
Autor/es:
ARROYO, DS; GAVIGLIO, EA; SORIA, JA; RODRIGUEZ-GALAN, MC; IRIBARREN, P
Lugar:
Mar del Plata, Argentina
Reunión:
Congreso; REUNIÓN ANUAL SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2009
Resumen:

Microglial cells (MC) are involved in central nervous system diseases. Our preliminary studies

have shown that after stimulation of MC with peptidoglycan of Staphylococcus aureus (PGN,

TLR2 agonist) several neurotoxic factors and MC death were induced.

Our goal was to study the mechanisms responsible of the cell death induced by PGN. Kinetic

studies of MC (BV2) treated with PGN showed the presence of AnnexinV/7AAD double positive

cell staining and low levels of early apoptotic cells (AnnexinV+), suggesting the presence of

necrosis. In addition, BV2 cells stimulated with PGN showed, by electronic microscopy, the

presence of double membrane vesicles (compatible with the ultrastructure of autophagic

vesicles) and strong vacuolization in the cell cytoplasm. These findings correlated with both a

particulated pattern of cytoplasmic staining with Monodansylcadaverine (MDC) and with

detection by western blot of clivated LC3B (LC3B II). These effects were inhibited by the

autophagy specific inhibitor, 3-Methyladenine (3 MA). Furthermore, we found a decrease of

BCL-2 protein (apoptosis and autophagy negative regulator) expression. Moreover the effects of

PGN were caspase 3 independent. These preliminary results suggest that PGN is able to

induce atypical MC death, probably by induction of exacerbated autophagy in a caspase 3-

independent manner.

Staphylococcus aureus (PGN,

TLR2 agonist) several neurotoxic factors and MC death were induced.

Our goal was to study the mechanisms responsible of the cell death induced by PGN. Kinetic

studies of MC (BV2) treated with PGN showed the presence of AnnexinV/7AAD double positive

cell staining and low levels of early apoptotic cells (AnnexinV+), suggesting the presence of

necrosis. In addition, BV2 cells stimulated with PGN showed, by electronic microscopy, the

presence of double membrane vesicles (compatible with the ultrastructure of autophagic

vesicles) and strong vacuolization in the cell cytoplasm. These findings correlated with both a

particulated pattern of cytoplasmic staining with Monodansylcadaverine (MDC) and with

detection by western blot of clivated LC3B (LC3B II). These effects were inhibited by the

autophagy specific inhibitor, 3-Methyladenine (3 MA). Furthermore, we found a decrease of

BCL-2 protein (apoptosis and autophagy negative regulator) expression. Moreover the effects of

PGN were caspase 3 independent. These preliminary results suggest that PGN is able to

induce atypical MC death, probably by induction of exacerbated autophagy in a caspase 3-

independent manner.