title: Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.
abstract: Therapeutic use and function of recombinant molecules can be studied by the expression of foreign genes in mice. In this study, we have expressed human Fcγ receptor-Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness with purified molecules in blocking immune-complex (IC)-mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16A(F)-Ig, CD32A(R)-Ig and CD32A(H)-Ig) reached a maximum of 130 μg ml(-1) of blood within 24 h after plasmid DNA administration. The in vivo half-life of FcγR-Igs was found to be 9-16 days and western blot analysis showed that the FcγR-Igs were expressed as a homodimer. The hydrodynamically expressed FcγR-Igs blocked 50-80% of IC-mediated inflammation up to 3 days in a reverse passive Arthus reaction model. Comparative analysis with purified molecules showed that hydrodynamically expressed FcγR-Igs are more efficient than purified molecules in blocking IC-mediated inflammation and had a higher half-life. In summary, these results suggest that the administration of a plasmid vector with the FcγR-Ig gene can be used to study the consequences of blocking IC binding to FcγRs during the development of inflammatory diseases. This approach may have potential therapeutic value in treating IC-mediated inflammatory autoimmune diseases such as lupus, arthritis and autoimmune vasculitis.
authors: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors: R
authors: R
authors: Shashidharamurthy
authors: D
authors: D
authors: Machiah
authors: E N
authors: EN
authors: Bozeman
authors: S
authors: S
authors: Srivatsan
authors: J
authors: J
authors: Patel
authors: A
authors: A
authors: Cho
authors: J
authors: J
authors: Jacob
authors: P
authors: P
authors: Selvaraj
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001183:Arthus Reaction / Q000235:genetics; D018014:Gene Transfer Techniques; D006207:Half-Life; D006801:Humans; D057446:Hydrodynamics; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000276:immunology; D051379:Mice; D010957:Plasmids; D017452:Receptors, IgG / Q000235:genetics*
chemical_list: D000936:Antigen-Antibody Complex; D018836:Inflammation Mediators; D017452:Receptors, IgG