Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance.
Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance.
复制标题
DOI：
10.1111/acel.12330
复制
发表时间：
2015-08
期刊：
影响因子：
7.8
通讯作者：
Santambrogio L
中科院分区：
文献类型：
--
作者：
Zolla V;Nizamutdinova IT;Scharf B;Clement CC;Maejima D;Akl T;Nagai T;Luciani P;Leroux JC;Halin C;Stukes S;Tiwari S;Casadevall A;Jacobs WR Jr;Entenberg D;Zawieja DC;Condeelis J;Fooksman DR;Gashev AA;Santambrogio L
淋巴管的作用是将液体、可溶性分子和免疫细胞输送到引流淋巴结。在这里，我们分析衰老过程如何影响淋巴管的功能和淋巴液流动的动态。超微结构、生化和蛋白质组学分析表明，老年收集器中基质蛋白和平滑肌细胞的损失导致收缩频率、收缩期淋巴流速和泵送活动降低（在淋巴收集器体内测量）。从功能上讲，这种损伤也转化为体内细菌转运能力的降低（通过延时显微镜测定）。超微结构和蛋白质组分析还表明，老年淋巴收集器的内皮细胞糖萼厚度减少，间隙连接蛋白丢失。氧化还原蛋白质组学分析描绘了淋巴管内皮细胞和基质蛋白的糖化和羧化与衰老相关的增加。从功能上讲，这些修饰转化为淋巴管明显的渗透性过高，病原体从收集器逃逸到周围组织，并降低了控制组织液稳态的能力。总而言之，我们的数据提供了对老化淋巴管中发生的解剖和生化变化如何损害淋巴液流动、组织液稳态和病原体运输的机制分析。
The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic’s endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport.