Muthuchamy Mariappan, Zawieja David
Department of Systems Biology and Translational Medicine, College of Medicine, Cardiovascular Research Institute Division of Lymphatic Biology, Texas A&M Health Science Center, College Station, TX 77843-1114, USA.
Ann N Y Acad Sci. 2008;1131:89-99. doi: 10.1196/annals.1413.008.
The lymphatic system plays critical roles in body fluid and macromolecular homeostasis, lipid absorption, immune function, and metastasis. To accomplish these tasks, the lymphatics must move lymph and its contents from the interstitial space through the lymph vessels and nodes and into the great veins. Contrary to popular belief, lymph does not passively "drain" down this pathway, because the net pressure gradients oppose flow. Instead, the lymphatics must act as both the conduits that direct and regulate lymph flow and the pumps that generate the lymph flow. Thus, to regulate lymph transport and function, both lymphatic pumping and flow resistance must be controlled. Both of these processes occur via regulation of lymphatic muscle contractions, which are classically thought to occur via the interaction of cell calcium with regulatory and contractile proteins. However, our knowledge of this regulation of lymphatic contractile function is far from complete. In this chapter we review our understanding of the important molecular mechanisms, the calcium regulation, and the contractile/regulatory proteins that control lymphatic contractions. A better understanding of these mechanisms could provide the basis for the development of better diagnostic and treatment modalities for lymphatic dysfunction. While progress has been made in our understanding of the molecular biology of lymphangiogenesis as a result of the development of potential lymphangiogenic therapeutic targets, there are currently no therapeutic agents that specifically modulate lymphatic pump function and lymph flow via lymphatic muscle. However, their development will not be possible until the molecular basis of lymphatic contractility is more fully understood.
淋巴系统在体液和大分子稳态、脂质吸收、免疫功能及转移过程中发挥着关键作用。为完成这些任务，淋巴管必须将淋巴及其所含物质从组织间隙通过淋巴管和淋巴结输送至大静脉。与普遍看法相反，淋巴并非被动地沿此路径“引流”，因为净压力梯度会阻碍淋巴流动。相反，淋巴管必须既充当引导和调节淋巴流动的管道，又作为产生淋巴流动的泵。因此，为调节淋巴运输和功能，必须控制淋巴泵血及流动阻力。这两个过程均通过调节淋巴管肌肉收缩来实现，传统观点认为，这一过程是通过细胞钙与调节蛋白及收缩蛋白的相互作用来完成的。然而，我们对淋巴管收缩功能调节的了解还远远不够。在本章中，我们将回顾对控制淋巴管收缩的重要分子机制、钙调节以及收缩/调节蛋白的理解。更好地理解这些机制可为开发针对淋巴管功能障碍的更好诊断和治疗方法提供依据。尽管由于潜在淋巴管生成治疗靶点的开发，我们对淋巴管生成分子生物学的理解取得了进展，但目前尚无通过淋巴管肌肉特异性调节淋巴泵功能和淋巴流动的治疗药物。然而，在更全面了解淋巴管收缩的分子基础之前，开发此类药物是不可能实现的。
