Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes
Modeling Lymph Flow and Fluid Exchange with Blood Vessels in Lymph Nodes
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DOI：
10.1089/lrb.2015.0028
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发表时间：
2015-12-01
影响因子：
1.4
通讯作者：
Moore, J. E., Jr.
中科院分区：
文献类型：
--
作者：
Jafarnejad, Mohammad;Woodruff, Matthew C.;Moore, J. E., Jr.
背景：淋巴结（LN）的位置在整个身体的淋巴过滤和免疫反应的关键介质的战略。淋巴携带细胞因子、抗原和细胞到下游LN，并且它们有效地递送到LN内的正确位置直接影响免疫应答的质量和数量。尽管这个系统的重要性，在LN的流动模式从来没有被量化，部分原因是实验表征是如此困难的。方法和结果：为了实现更定量的知识LN流，计算流模型已开发的基础上，小鼠腘LN，允许参数敏感性分析，以确定重要的系统特性。该模型表明，约90%的淋巴液通过包膜下和髓窦的外周路径，而灌注到副皮质更深处的液体被实质血管隔离。在基线条件下，这些血管的液体吸收主要由淋巴和血液之间的压力差驱动，尽管液体转移的幅度高度依赖于血管表面积。我们还预测，液压传导率的髓质，一个参数，从来没有被实验测量，应该是至少三个数量级大于的paracortex，以确保生理压力在node.Conclusions：这些结果表明，在LN微环境的结构变化，以及流入/流出条件的变化，显着改变淋巴，细胞因子，抗原和细胞内的LN的分布，具有很大的潜力，调节免疫反应。
Background:Lymph nodes (LNs) are positioned strategically throughout the body as critical mediators of lymph filtration and immune response. Lymph carries cytokines, antigens, and cells to the downstream LNs, and their effective delivery to the correct location within the LN directly impacts the quality and quantity of immune response. Despite the importance of this system, the flow patterns in LN have never been quantified, in part because experimental characterization is so difficult.Methods and Results:To achieve a more quantitative knowledge of LN flow, a computational flow model has been developed based on the mouse popliteal LN, allowing for a parameter sensitivity analysis to identify the important system characteristics. This model suggests that about 90% of the lymph takes a peripheral path via the subcapsular and medullary sinuses, while fluid perfusing deeper into the paracortex is sequestered by parenchymal blood vessels. Fluid absorption by these blood vessels under baseline conditions was driven mainly by oncotic pressure differences between lymph and blood, although the magnitude of fluid transfer is highly dependent on blood vessel surface area. We also predict that the hydraulic conductivity of the medulla, a parameter that has never been experimentally measured, should be at least three orders of magnitude larger than that of the paracortex to ensure physiologic pressures across the node.Conclusions:These results suggest that structural changes in the LN microenvironment, as well as changes in inflow/outflow conditions, dramatically alter the distribution of lymph, cytokines, antigens, and cells within the LN, with great potential for modulating immune response.