Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.
Hydrodynamic delivery of plasmid DNA encoding human FcγR-Ig dimers blocks immune-complex mediated inflammation in mice.
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作者：
重组分子的治疗用途和功能可以通过外源基因在小鼠体内的表达来研究。在本研究中，我们用FcγR-Ig融合分子(FcγR-Ig)在小鼠体内进行了流体力学表达，并与纯化的分子阻断免疫复合物(IC)介导的炎症反应的效果进行了比较。γR-IGs(CD16AF-Ig、CD32AR-Ig和CD32AH-Ig)在给药后24 h内血药浓度最高可达130μg/ml。FcγR-Ig在体内的半衰期为9~16天，Western印迹分析表明FcγR-Ig以同源二聚体形式表达。在反向被动阿尔萨斯反应模型中，流体力学表达的Fc-γR-Ig可阻止50-80%的IC介导的炎症反应，最长可达3天。与纯化分子的比较分析表明，流体力学表达的Fc、γ、R-Igs在阻断IC介导的炎症方面比纯化分子更有效，并且具有更高的半衰期。综上所述，这些结果表明，携带FcγR-Ig基因的质粒载体可用于研究在炎症性疾病的发展过程中阻断与FcγR的IC结合的后果。这种方法可能在治疗IC介导的炎症性自身免疫性疾病如狼疮、关节炎和自身免疫性血管炎方面具有潜在的治疗价值。
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 Fcgamma receptor –Ig fusion molecules (FcγR-Igs) in mice by administering FcγR-Ig plasmid DNAs hydrodynamically and compared their effectiveness to purified molecules in blocking immune-complex (IC) mediated inflammation in mice. The concentration of hydrodynamically expressed FcγR-Igs (CD16AF-Ig, CD32AR-Ig and CD32AH-Ig) reached a maximum of 130 μg/ml 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 a 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.
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影响因子：
4.4
作者：
Chang, He;Hanawa, Haruo;Aizawa, Yoshifusa
通讯作者：
Aizawa, Yoshifusa
影响因子：
4.2
作者：
He, YK;Pimenov, AA;Huang, L
通讯作者：
Huang, L
影响因子：
3.5
作者：
Budker, Vladimir G.;Subbotin, Vladimir M.;Wolff, Jon A.
通讯作者：
Wolff, Jon A.
DOI：
10.1073/pnas.93.11.5512
发表时间：
1996-05-28
影响因子：
11.1
作者：
Junghans, RP;Anderson, CL
通讯作者：
Anderson, CL
影响因子：
158.5
作者：
CLARKSON, SB;BUSSEL, JB;UNKELESS, JC
通讯作者：
UNKELESS, JC