Immune Responses to Biosurfaces

Diana Karpman, Anne-lie Ståhl, Ida Arvidsson, Karl Johansson, Sebastian Loos, Ramesh Tati, Zivile Békássy, Ann-Charlotte Kristoffersson, Maria Mossberg, Robin Kahn, Karpman, Diana, Ståhl, Anne-lie, Arvidsson, Ida, Johansson, Karl, Loos, Sebastian, Tati, Ramesh, Békássy, Zivile, Kristoffersson, Ann-Charlotte, Mossberg, Maria, Kahn, Robin

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.