Regulatory control of the terminal complement proteins at the surface of
human endothelial cells: neutralization of a C5b-9 inhibitor by antibody to
CD59
KK Hamilton, Z Ji, S Rollins, BH Stewart and PJ Sims
Cardiovascular Biology Research Program, Oklahoma Medical Research
Foundation, Oklahoma City 73104.
Functionally inhibitory antibody to the plasma membrane complement
inhibitor CD59 has been used to investigate control of the terminal
complement proteins at the endothelial cell surface. Antibodies against
purified human erythrocyte CD59 (polyclonal anti-CD59 and monoclonal
antibodies [MoAbs] 1F1 and 1F5) were found to bind specifically to
monolayers of cultured human umbilical vein endothelial cells, and by
Western blotting to recognize an 18- to 21-Kd endothelial protein. When
bound to the endothelial monolayer, anti-CD59 (immunoglobulin G or Fab
fragment) potentiated membrane pore formation induced upon C9 binding to
C5b-8, and augmented the C5b-9-induced cellular responses, including
stimulated secretion of von Willebrand factor and expression of catalytic
surface for the prothrombinase enzyme complex. Although potentiating
endothelial responses to the terminal complement proteins, anti-CD59 had no
effect on the response of these cells to stimulation by histamine. Taken
together, these data suggest that human endothelial cells express the CD59
cell surface inhibitor of the terminal complement proteins, which serves to
protect these cells from pore- forming and cell-stimulatory effects of the
C5b-9 complex. These data also suggest that the inactivation or deletion of
this cell surface regulatory molecule would increase the likelihood for
procoagulant changes in endothelium exposed to complement activation in
plasma.
Volume 76,
Issue 12,
pp. 2572-2577,
12/15/1990
Copyright © 1990 by The American Society of Hematology
