A. Vakeva et S. Meri, Complement activation and regulator expression after anoxic injury of human endothelial cells, APMIS, 106(12), 1998, pp. 1149-1156
Complement activation is involved in the ischemia-reperfusion injury of var
ious organs, but the mechanisms leading to activation of the complement sys
tem are incompletely understood. In this study we show that EA.hy 926 human
endothelial cells cultured under anoxic conditions (24 or 48 h) become act
ivators of the homologous complement system. Flow cytometric analysis indic
ated that Clq, C3c, C3d, C4, C5, C9 components of complement are deposited
on anoxic but not on normoxic cells after incubation with normal human seru
m. Cell membrane-associated regulators of complement, membrane cofactor pro
tein (CD46), decay-accelerating factor (CD55) and protectin (CD59) were exp
ressed on EA.hy 926 cells grown under normal oxygen tension. Under anoxic c
onditions the expression of protectin was clearly decreased, whereas the ex
pression of CD46 and CD55 diminished only slightly. Our results suggest tha
t anoxia can convert human endothelial cells to activators of the complemen
t system. The diminished expression of protectin, CD46 and CD55 can sensiti
ze the cells to complement-mediated damage. Activation of the complement sy
stem due to the anoxic injury of human endothelial cells might be an import
ant triggering mechanism in the pathogenesis of ischemia-reperfusion injury
of human heart.