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

Abstract

Damage of the endothelium as a result of activation of the complement system is one of the causes of thrombotic complications in COVID-19. Factor C3 plays a key role in this process. The attachment of its proteolytic product C3b to the cells initiates the formation of the membrane attack complex C5b-9, which forms a pore in the plasma membrane and cell death. Here, we investigated how histamine, secreted in the body by leukocytes and mast cells, can affect the binding of C3b to human umbilical vein endothelial cells (HUVEC). To visualize it, FITS-conjugated antibodies against the C3c were used. These antibodies bind to intact C3 and to C3b but not to C3a. We have shown that when cultured HUVECs are incubated with human blood plasma, factor C3/C3b accumulates in the form of rounded and diffuse foci on the surface of the endothelial cell monolayer. Pre-activation of HUVEC by histamine increases the number of С3/C3b attachment sites. These data suggest that histamine may enhance endothelial damage during complement hyperactivation in COVID-19 and in endotheliopathies caused by other diseases.