Witte M H, Bernas M J, Martin C P, Witte C L
Department of Surgery, The University of Arizona College of Medicine, Tucson, Arizona 85724-5063, USA.
Microsc Res Tech. 2001 Oct 15;55(2):122-45. doi: 10.1002/jemt.1163.
The lymph vascular system parallels the blood vasculature and as one of its key functions returns liquid and solutes to the bloodstream, including macromolecules that have escaped from blood capillaries and entered the interstitium. In conjunction with interspersed lymph nodes and lymphoid organs, the lymphatic vasculature also acts as a conduit for trafficking immune cell populations. Echoing the explosion of knowledge about blood vessel angiogenesis (properly termed "hemangiogenesis"), the past two decades have also witnessed a series of significant, yet less-noticed discoveries bearing on "lymphangiogenesis," along with delineation of the spectrum of lymphedema-angiodysplasia syndromes. Failure of lymph transport promotes a brawny proteinaceous edema of the affected limb, organ, or serous space that is disfiguring, disabling, and on occasion even life-threatening. Key members of the vascular endothelial growth factor (VEGF) and angiopoietin families of vascular growth factors (and their corresponding tyrosine kinase endothelial receptors) have been identified which preferentially influence lymphatic growth and, when manipulated in genetically engineered murine models, produce aberrant "lymphatic phenotypes." Moreover, mutations in VEGF receptor and forkhead family developmental genes have now been linked and implicated in the pathogenesis of two familial lymphedema-angiodysplasia syndromes. Thus, recent advances in "molecular lymphology" are elucidating the poorly understood development, physiology, and pathophysiology of the neglected lymphatic vasculature. In combination with fresh insights and refined tools in "clinical lymphology," these advances should lead not only to earlier detection and more rational classification of lymphatic disease but also to better therapeutic approaches, including designer drugs for lymphangiostimulation and lymphangioinhibition and gene therapy to modulate lymphatic growth.
淋巴系统与血液循环系统并行，其关键功能之一是将液体和溶质，包括从毛细血管逸出并进入间质的大分子，返回血液循环。与散布的淋巴结和淋巴器官一起，淋巴管系统还充当免疫细胞群体运输的管道。随着关于血管生成（正确称为“血管新生”）知识的激增，在过去二十年中也见证了一系列关于“淋巴管生成”的重大但较少被关注的发现，以及对淋巴水肿 - 血管发育异常综合征谱的描述。淋巴运输功能障碍会导致受影响的肢体、器官或浆膜腔出现严重的蛋白质性水肿，这种水肿会导致容貌受损、功能障碍，甚至有时会危及生命。已鉴定出血管内皮生长因子（VEGF）和血管生成素家族的血管生长因子的关键成员（及其相应的酪氨酸激酶内皮受体），它们优先影响淋巴生长，并且在基因工程小鼠模型中进行操作时会产生异常的“淋巴管表型”。此外，VEGF受体和叉头家族发育基因的突变现在已与两种家族性淋巴水肿 - 血管发育异常综合征的发病机制相关联并被认为与之有关。因此，“分子淋巴学”的最新进展正在阐明人们了解甚少的被忽视的淋巴管系统的发育、生理学和病理生理学。结合“临床淋巴学”中的新见解和改进工具，这些进展不仅应能实现对淋巴疾病的更早检测和更合理分类，还应能带来更好的治疗方法，包括用于淋巴管刺激和淋巴管抑制的定制药物以及调节淋巴生长的基因治疗。
