Mast cells are potent immune sensors of the tissue microenvironment. Within seconds of activation, they release various preformed biologically active products and initiate the process of de novo synthesis of cytokines, chemokines, and other inflammatory mediators. This process is regulated at multiple levels. Besides the extensively studied IgE and IgG receptors, toll-like receptors, MRGPR, and other protein receptor signaling pathways, there is a critical activation pathway based on cholesterol-dependent, pore-forming cytolytic exotoxins produced by Gram-positive bacterial pathogens. This pathway is initiated by binding the exotoxins to the cholesterol-rich membrane, followed by their dimerization, multimerization, pre-pore formation, and pore formation. At low sublytic concentrations, the exotoxins induce mast cell activation, including degranulation, intracellular calcium concentration changes, and transcriptional activation, resulting in production of cytokines and other inflammatory mediators. Higher toxin concentrations lead to cell death. Similar activation events are observed when mast cells are exposed to sublytic concentrations of saponins or some other compounds interfering with the membrane integrity. We review the molecular mechanisms of mast cell activation by pore-forming bacterial exotoxins, and other compounds inducing cholesterol-dependent plasma membrane perturbations. We discuss the importance of these signaling pathways in innate and acquired immunity.

• MeSH
• buněčná membrána imunologie   metabolismus   mikrobiologie   patologie   MeSH
• buněčná smrt MeSH
• buněčné mikroprostředí MeSH
• cholesterol metabolismus   MeSH
• cytokiny metabolismus   MeSH
• cytotoxiny metabolismus   MeSH
• degranulace buněk MeSH
• grampozitivní bakteriální infekce imunologie   metabolismus   mikrobiologie   patologie   MeSH
• grampozitivní bakterie imunologie   metabolismus   MeSH
• interakce hostitele a patogenu MeSH
• lidé MeSH
• mastocyty imunologie   metabolismus   mikrobiologie   patologie   MeSH
• mediátory zánětu metabolismus   MeSH
• vápníková signalizace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH