Activation of Complement Factor C3/C3b Deposition on the of Endothelial Cell Surface by Histamine As one of the Causes of Endothelium Damage in COVID-19

Abstract

Endothelial damage as a result of complement system activation is one of the causes of thrombotic complications in COVID-19. Factor C3 plays a key role in this process. The attachment of its proteolysis product C3b to the membrane initiates the beginning of the formation of membrane attack complex C5b-9, which forms a pore in the plasma membrane and cell death. In the present study, we investigated how histamine, secreted in the body at sites of inflammation by leukocytes and mast cells, might affect the binding of C3b to endothelial cells (ECs). FITS-conjugated antibodies against the C3c fragment were used to visualize it. These antibodies bind to intact C3 and to C3b but not to C3a. We have shown that incubation of human blood plasma with cultured ECs from human umbilical vein results in accumulation of C3/C3b as rounded local and diffuse foci on the surface of the cell monolayer. Pre-activation of ECs by histamine increases the number of C3/C3b attachment sites. These data suggest that histamine can enhance endothelial layer damage during hyperactivation of the complement system in COVID-19 and endotheliopathies caused by other diseases.