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A novel liposome based delivery system to bolster membrane‐bound anti‐complement defenses is highly effective against complement activation via the classical pathway
Author(s) -
Goga Ledia,
Olson Paul K,
PerezAbadia Gustavo,
Anderson Gary L,
Barker John H,
Maldonado Claudio
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.lb89-a
Subject(s) - complement system , biotinylation , c3 convertase , alternative complement pathway , liposome , transplantation , microbiology and biotechnology , chemistry , membrane , lipid bilayer fusion , cell , antibody , immunology , medicine , biochemistry , biology , surgery
Excessive complement (C) activation due to ischemia/reperfusion following organ transplantation has been associated with graft dysfunction. A number of anti‐C agents have been developed; however, systemic administration of these leaves recipients vulnerable to infection. To develop a targeted therapy we created a novel method to decorate cells with proteins by using fusogenic lipid vesicles (FLVs) that fuse with cells and incorporate their lipids into cell membranes. These lipids contain biotin tethers which link with fusion proteins containing streptavidin (SA). The purpose of this study was to develop an anti‐C targeted therapy in which the C3 convertase inhibitor vaccinia virus C control protein (VCP) was combined with SA (SA‐VCP). We hypothesized that cells decorated with SA‐VCP would reduced C3b deposition after C activation. Studies were conducted in human fibroblasts and SKOV‐3 cells. Biotinylation of cells were optimized by adjusting FLV formulation, and by determining the ideal incubation times and levels of FLVs. Trastuzimab and human serum were used for C activation, and C3b deposition was measured using a microplate reader. We found that SA‐VCP treatment significantly (p<0.001) reduced C3b deposition compared to controls. We conclude that membrane display of anti‐C proteins is effective in reducing C deposition, and that this therapy has potential in transplantation. NIH funded R41 HL079855.