In vivo diffusion of immunoglobulin G in muscle: effects of binding, solute exclusion, and lymphatic removal
In vivo diffusion of immunoglobulin G in muscle: effects of binding, solute exclusion, and lymphatic removal
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DOI：
10.1152/ajpheart.1997.273.6.h2783
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发表时间：
1997-12-01
影响因子：
4.8
通讯作者：
Zakaria, ER
中科院分区：
文献类型：
--
作者：
Flessner, MF;Lofthouse, J;Zakaria, ER
以前，我们证明了免疫球蛋白G（IgG）在腹腔内溶解于等渗溶液中，当腹腔内压>2 cmH（2）O时，可迅速转运到腹壁。我们假设这主要是由对流引起的，IgG的扩散可以忽略不计。为了研究扩散的作用，我们用含有I-125标记的IgG的ip等渗溶液透析大鼠，在没有压力梯度的情况下通过腹壁肌肉2或6小时。在实验结束时，将动物安乐死并冷冻，处理腹壁组织以产生横截面放射自显影。定量光密度分析导致IgG浓度曲线的幅度远低于对流占主导地位的实验中的曲线。在其他体内实验中，我们确定淋巴液流速为0.8 × 10（-4）ml min（-1）.g（-1），IgG可利用的血管外组织分数（θ）为0.041 +/-0.001。采用体外结合试验测定时间依赖性、非饱和结合常数：0.0065 min（-1）x暴露持续时间。将包括θ效应、时间依赖性结合和淋巴流的非稳态扩散模型与扩散曲线数据拟合，组织空隙内的IgG扩散率估计为2 x 10（-7）cm（2）/s，该值远高于其他研究组发表的值。我们还从我们以前的数据表明，IgG通过组织的对流在ip压力>2 cmH（2）O时占主导地位，但扩散可能是不可忽略的。此外，在解释组织蛋白浓度分布时，必须考虑非饱和结合。
Previously, we demonstrated that immunoglobulin G (IgG), dissolved in an isotonic solution in the peritoneal cavity, transported rapidly into the abdominal wall when the intraperitoneal tip) pressure was >2 cmH(2)O. We hypothesized that this was chiefly caused by convection and that diffusion of IgG was negligible. To investigate the role of diffusion, we dialyzed rats with no pressure gradient across the abdominal wall muscle for 2 or 6 h with an ip isotonic solution containing I-125-labeled IgG. At the end of the experiment, ment, the animal was euthanized and frozen and abdominal wall tissue was processed to produce cross-sectional autoradiograms. Quantitative densitometric analysis resulted in IgG concentration profiles with far lower magnitude than profiles from experiments in which convection dominated. In other in vivo experiments, we determined the lymph flow rate to be 0.8 x 10(-4) ml min(-1).g(-1) and the fraction of extravascular tissue (theta(s)) available to the IgG to be 0.041 +/- 0.001. An in vitro binding assay was used to determine the time-dependent, nonsaturable binding constant: 0.0065 min(-1) x duration of exposure. A non-steady-state diffusion model that included effects of theta(s), time-dependent binding, and lymph flow was fitted to the diffusion profile data, and the IgG diffusivity within the tissue void was estimated to be 2 x 10(-7) cm(2)/s, a value much higher than that published by other groups. We also demonstrate from our previous data that convection of IgG through tissue dominates over diffusion at ip pressures >2 cmH(2)O, but diffusion may not be negligible. Furthermore, nonsaturable binding must be accounted for in the interpretation of tissue protein concentration profiles.