Triantafilou, K. ![]() ![]() ![]() ![]() |
Abstract
The membrane attack complex of complement (MAC), apart from its classical role of lysing cells, can also trigger a range of non-lethal effects on cells, acting as a drive to inflammation. In the present study, we chose to investigate these non-lethal effects on inflammasome activation. We found that, following sublytic MAC attack, there is increased cytosolic Ca2+ concentration, at least partly through Ca2+ release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) channels. This increase in intracellular Ca2+ concentration leads to Ca2+ accumulation in the mitochondrial matrix via the ‘mitochondrial calcium uniporter’ (MCU), and loss of mitochondrial transmembrane potential, triggering NLRP3 inflammasome activation and IL-1β release. NLRP3 co-localises with the mitochondria, probably sensing the increase in calcium and the resultant mitochondrial dysfunction, leading to caspase activation and apoptosis. This is the first study that links non-lethal effects of sublytic MAC attack with inflammasome activation and provides a mechanism by which sublytic MAC can drive inflammation and apoptosis.
Item Type: | Article |
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Date Type: | Published Online |
Status: | Published |
Schools: | Medicine |
Publisher: | Company of Biologists |
ISSN: | 0021-9533 |
Date of Acceptance: | 27 March 2013 |
Last Modified: | 24 Oct 2022 08:04 |
URI: | https://orca.cardiff.ac.uk/id/eprint/116742 |
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