Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice

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 Fc gamma receptor-Ig fusion molecules (Fc gamma R-Igs) in mice by administering Fc gamma R-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 Fc gamma R-Igs (CD16A(F)-Ig, CD32A(R)-Ig and CD32A(H)-Ig) reached a maximum of 130 mu g ml(-1) of blood within 24 h after plasmid DNA administration. The in vivo half-life of Fc gamma R-Igs was found to be 9-16 days and western blot analysis showed that the Fc gamma R-Igs were expressed as a homodimer. The hydrodynamically expressed Fc gamma R-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 Fc gamma R-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 Fc gamma R-Ig gene can be used to study the consequences of blocking IC binding to Fc gamma Rs 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.