Vaccinia virus complement control protein is capable of protecting xenoendothelial cells from antibody binding and killing by human complement and cytotoxic cells
F. Al-mohanna et al., Vaccinia virus complement control protein is capable of protecting xenoendothelial cells from antibody binding and killing by human complement and cytotoxic cells, TRANSPLANT, 71(6), 2001, pp. 796-801
Background.Vaccinia virus complement control protein (VCP) was the first se
cretory microbial protein shown to have structural similarity to the family
of complement control proteins, VCP can block both the classical and alter
nate complement pathways. Recently, VCP has been shown to bind to heparin,
and this property contributes to separate functions, making the molecule a
multifunctional protein.
Methods. VCP prepared from a natural infection of RK-13 cells with vaccinia
virus was purified to homogeneity, Cultured pig aortic endothelial cells (
PAECs) were mixed with human serum, anti-Gal alpha1,3 Gal antibody, neutrop
hils, or natural killer (NK) cells in the presence or absence of VCP and ei
ther direct binding of FITC-labeled antibody or billing by cytotoxic cells
was estimated,
Results. Our cell culture studies demonstrate that VCP blocks complement-me
diated killing of PAECs by human serum in a dose-dependent manner. We also
demonstrate that VCP is capable of blocking Gal alpha1,3 Gal binding sites
on PAECS, Surprisingly, VCP effectively blocked interactions between PAECs
and cytotoxic cells such as human naive neutrophils and NR cells.
Conclusion. VCP is a novel protein amongst the complement control protein f
amily and can, not only block xenorejection by inhibiting complement but al
so by blocking killing by cytotoxic cells.