Caspase-9/-3 activation and apoptosis are induced in XXXX macrophages upon ingestion and digestion of @entity526 bacteria.

@entity19 @entity185 @entity7349 @entity4699 @entity5001 @entity1379 @entity637 @entity526
A number of highly virulent, intracellular bacteria are known to induce cell death by apoptosis in infected host cells. In this work we demonstrate that phagocytosis of bacteria from the @entity526 laboratory strain K12 DH5alpha is a potent cell death stimulus for @entity19 macrophages. RAW264.7 @entity19 macrophages took up bacteria and digested them within 2-4 h as investigated with green fluorescent protein-expressing bacteria. No evidence of apoptosis was seen at 8 h postexposure, but at 24 h approximately 70% of macrophages displayed an apoptotic phenotype by a series of parameters. Apoptosis was blocked by inhibition of caspases or by forced expression of the apoptosis-inhibiting protein @entity1379 . Processing of @entity185 and @entity7349 but not @entity4699 was seen suggesting that the mitochondrial branch of the apoptotic pathway was activated. Active effector caspases could be detected in two different assays. Because the adapter molecule @entity5001 ( @entity5001 ) has been implicated in apoptosis, involvement of the Toll-like receptor pathway was investigated. In RAW264.7 cells, heat-treated bacteria were taken up poorly and failed to induce significant apoptosis. However, cell activation was almost identical between live and heat-inactivated bacteria as measured by extracellular signal-regulated kinase activation, generation of free radicals, and @entity637 secretion. Furthermore, primary bone marrow-derived macrophages from wild-type as well as from @entity5001 -deficient @entity19 underwent apoptosis upon phagocytosis of bacteria. These results show that uptake and digestion of bacteria leads to @entity5001 -independent apoptosis in @entity19 macrophages. This form of cell death might have implications for the generation of the immune response.
