Blood, Vol. 93 No. 7 (April 1), 1999:
pp. 2297-2301
Interaction Between Terminal Complement Proteins C5b-7 and Anionic
Phospholipids
Clive Liu,
Patricia Marshall,
Ian Schreibman,
Ann Vu,
Weiming Gai, and
Michael Whitlow
From the Division of Dermatology, Manhattan Veteran's Administration
Medical Center, New York; and Ronald O. Perelman Department of
Dermatology, New York University School of Medicine, New York,
NY.
We have recently shown that C5b-6 binds to the erythrocyte membrane
via an ionic interaction with sialic acid before the addition of C7 and
subsequent membrane insertion. In this study we assessed the role of
anionic lipids in the binding of the terminal complement proteins to
the membrane and the efficiency of subsequent hemolysis. Human
erythrocytes were modified by insertion of dipalmitoyl
phosphatidylcholine (DPPC), dipalmitoyl phosphatidylserine (DPPS),
dipalmitoyl phosphatidylethanolamine (DPPE), or dipalmitoyl
phosphatidic acid (DPPA). Lipid incorporation and the hemolytic assays
were done in the presence of 100 µmol/L sodium orthovanadate to
prevent enzymatic redistribution of lipid. We found that the neutral
lipids, DPPC and DPPE, did not affect C5b-7 uptake or hemolysis by
C5b-9. In contrast, the two acidic phospholipids, DPPS and DPPA, caused
a dose-dependent increase in both lysis and C5b-7 uptake. We conclude
that the presence of anionic lipids on the exterior face of the
membrane increases C5b-7 uptake and subsequent hemolysis. It is known
that sickle cell erythrocytes have increased exposure of
phosphatidylserine on their external face and are abnormally sensitive
to lysis by C5b-9. The data presented here provide a plausible
mechanism for this increased sensitivity.
