Yp. Li et al., SUBLYTIC COMPLEMENT ATTACK EXPOSES C-REACTIVE PROTEIN-BINDING SITES ON CELL-MEMBRANES, The Journal of immunology, 152(6), 1994, pp. 2995-3005
C-reactive protein (CRP) is an acute phase serum protein synthesized b
y the liver. CRP has been localized to acute inflammatory sites and ha
s been postulated to facilitate the removal of damaged cells. CRP bind
s to a number of ligands that may be present in inflammatory sites, an
d the extent to which individual ligands are involved in its binding t
o tissue sites is unknown. Complement activation is important in the t
issue damage in many inflammatory conditions causing cell membrane dam
age and recruitment of inflammatory cells. This paper describes the bi
nding of CRP to complement-damaged cell membranes. Raji cells activate
the alternative complement pathway resulting in the deposition of C3b
and membrane attack complexes (MAC) on the cell membrane. However, Ra
ji cells are relatively resistant to killing by human complement. Trea
tment of Raji cells with human serum led to calcium-dependent phosphoc
holine-inhibitable CRP binding. CRP binding was eliminated by depletio
n of C3, C5, or C8 and reduced by depletion of C9 from serum. CRP bind
ing preceded cell death and co-localized with MAC on cell membranes. C
RP binding to complement-treated liposomes required phosphatidylcholin
e in addition to the MAC indicating that membrane phospholipids rather
than the MAC proteins provide the binding sites for CRP. However, for
both liposomes and Raji cells disruption of the lipid bilayer by comp
lement attack was required for CRP binding to occur. These results sup
port the hypothesis that CRP binding at sites of inflammation may be m
ediated by exposed phospholipids on damaged cell membranes.