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Complement Interactions with Blood Cells, Endothelial Cells and Microvesicles in Thrombotic and Inflammatory Conditions

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Immune Responses to Biosurfaces

Abstract

The complement system is activated in the vasculature during thrombotic and inflammatory conditions. Activation may be associated with chronic inflammation on the endothelial surface leading to complement deposition. Complement mutations allow uninhibited complement activation to occur on platelets, neutrophils, monocytes, and aggregates thereof, as well as on red blood cells and endothelial cells. Furthermore, complement activation on the cells leads to the shedding of cell derived-microvesicles that may express complement and tissue factor thus promoting inflammation and thrombosis. Complement deposition on red blood cells triggers hemolysis and the release of red blood cell-derived microvesicles that are prothrombotic. Microvesicles are small membrane vesicles ranging from 0.1 to 1 μm, shed by cells during activation, injury and/or apoptosis that express components of the parent cell. Microvesicles are released during inflammatory and vascular conditions. The repertoire of inflammatory markers on endothelial cell-derived microvesicles shed during inflammation is large and includes complement. These circulating microvesicles may reflect the ongoing inflammatory process but may also contribute to its propagation. This overview will describe complement activation on blood and endothelial cells and the release of microvesicles from these cells during hemolytic uremic syndrome, thrombotic thrombocytopenic purpura and vasculitis, clinical conditions associated with enhanced thrombosis and inflammation.

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Acknowledgements

This work was supported by grants from The Swedish Research Council (K2013-64X-14008 and K2015-99X-22877-01-6), The Torsten Söderberg Foundation, The Konung Gustaf V:s 80-årsfond, SUS stiftelser och donationer (all to DK). The Swedish Renal foundation (to ZB) and the Fanny Ekdahl Foundation (to ZB and RK). Crown Princess Lovisa’s Society for Child Care (to DK and RK), Alfred Österlund’s Foundation, Greta and Johan Kock’s Foundation, the Samariten Foundation, and the Royal Physiographic Society (all to RK). SL was supported by a research fellowship from the Deutsche Forschungsgemeinschaft (LO 2021/2-1).

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Karpman, D. et al. (2015). Complement Interactions with Blood Cells, Endothelial Cells and Microvesicles in Thrombotic and Inflammatory Conditions. In: Lambris, J., Ekdahl, K., Ricklin, D., Nilsson, B. (eds) Immune Responses to Biosurfaces. Advances in Experimental Medicine and Biology, vol 865. Springer, Cham. https://doi.org/10.1007/978-3-319-18603-0_2

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