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Stimulation of platelet apoptosis by peptidoglycan from Staphylococcus aureus 113.
- Source :
-
Apoptosis : an international journal on programmed cell death [Apoptosis] 2012 Sep; Vol. 17 (9), pp. 998-1008. - Publication Year :
- 2012
-
Abstract
- Peptidoglycan (PGN), a component of bacterial cell wall and belonging to "Microbe-Associated Molecular Patterns" (MAMP) triggers host reactions contributing to the pathophysiology of infectious disease. Host cell responses to PGN exposure include apoptosis. Bacterial infections may result in activation of blood platelets and thrombocytopenia. The present study explored, whether HPLC-purified fractions of PGNs from Staphylococcus aureus 113 triggers apoptosis of platelets. To this end platelets were exposed to PGN fractions and annexin-V binding determined to depict cell membrane scrambling, DiOC6 fluorescence to estimate depolarization of mitochondrial potential, Fluo-3AM staining for intracellular Ca(2+) activity ([Ca(2+)](i)) and immunofluorescence to quantify protein abundance of active caspase-3. As a result, a 30 min exposure to monomeric fraction (mPGN) (≥50 ng/ml) was followed by annexin-V binding, paralleled by increase of [Ca(2+)](i), mitochondrial depolarization, caspase-3 activation and integrin α(IIb)β(3) upregulation. The annexin-V binding was significantly blunted by anti-TLR-2 antibodies, in absence of extracellular Ca(2+), and by pancaspase inhibitor zVAD-FMK (1 μM). In conclusion, PGN triggers apoptosis of platelets in activation-dependent manner, characterized by mitochondrial depolarization, caspase-3 activation and cell membrane scrambling.
- Subjects :
- Amino Acid Chloromethyl Ketones pharmacology
Annexin A5 metabolism
Antibodies immunology
Caspase 3 metabolism
Caspase Inhibitors pharmacology
Cell Membrane drug effects
Cell Membrane metabolism
Cells, Cultured
Enzyme Activation
Humans
Integrin alpha2 biosynthesis
Mitochondria metabolism
Toll-Like Receptor 2 immunology
Apoptosis drug effects
Blood Platelets drug effects
Blood Platelets metabolism
Peptidoglycan pharmacology
Staphylococcus aureus chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1573-675X
- Volume :
- 17
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Apoptosis : an international journal on programmed cell death
- Publication Type :
- Academic Journal
- Accession number :
- 22752708
- Full Text :
- https://doi.org/10.1007/s10495-012-0718-1