Complement Activation, Immunogenicity, and Immune Suppression as Potential Side Eff ects of Liposomes - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 315

The second major cause underlying the immune recognition of
liposomes is the lack of self-discriminating molecules on the bilayer
membrane. Figure 11.3 shows those that are engaged in protecting
cells from attack by the C system, referred to as C control proteins
(CCPs). These include C receptor type 1 (CR1), decay accelerating
factor (DAF), membrane cofactor protein (MCP) and CD59.
Figure 11.3 Complement control proteins on blood cells, endothelial and
other cells that normally prevent host damage by C attack. They are not
present on current liposomes (reproduced from [44] with permission).
Figure 11.3 also illustrates the activities of these proteins [44]:
CR1 binds C3b and C4b and promotes their physical dissociation
(decay accelerating activity). Furthermore, CR1 also enhances the
catalytic lysis of C3 convertases by the plasma serine protease, factor
I (fI) (cofactor activity). Furthermore, CR1 binds C3b-opsonised
particles and immune complexes, extracting them from the activation
cascade and carrying them to -among others, to cells of the RES.
DAF binds C3 convertase and accelerates its decay to subunits; MCP
displays fI-cofactor activity, while CD59, as the last defense line
against C damage, interferes with C9 unfolding and polymerizing
to form the membrane attack complex (MAC) [44]. In the absence
of the above membrane proteins, which normally prevent host
damage by C attack, the mistake of the immune system to recognize
beneficial liposomal medicines becomes irreversible “friendly fire.”
The ensuing inflammatory reaction causes harm to both the body
and the liposomal drug.