Ratajska Anna, Jankowska-Steifer Ewa, Czarnowska Elżbieta, Flaht Aleksandra, Radomska-Leśniewska Dorota
Katedra i Zakład Patomorfologii Warszawskiego Uniwersytetu Medycznego, ul. T. Chałubińskiego 5, 02-004 Warszawa, Poland.
Postepy Hig Med Dosw (Online). 2012 Nov 19;66:901-12. doi: 10.5604/17322693.1020753.
In this paper, we present literature results related to structure and various manners of lymphatic vessel formation during embryonic development and in pathological events, such as tumorigenesis, wound healing, and other diseases. The functions of the lymphatic system include the collection of fluids that enter tissues from the circulation, absorption of lipids and lipid-soluble vitamins from the intestine and their subsequent transport, participation in antigen, dendritic cell, and lymphocyte migration. The lymphatic system is also a route for tumor cell and inflammatory cell transport. Native lymphatic capillaries differ from blood capillaries by having an irregular lumen, a discontinuous basement membrane, absence of pericytes, and a strong anchorage of their endothelial cells to the extracellular matrix via microfibrils built of emilin and fibrillin. Lymphatic endothelial cells express surface antigens such as Lyve-1, podoplanin, VEGFR3 (Flk4) and transcription factor Prox-1, as well as molecules which are common for blood endothelial cells and lymphatic endothelial cells (CD31, CD34, Flk-1, Tie-1, Tie-2, neuropilin 2). Lymphatic vessel formation during embryonic development starts with the occurrence of lymphatic sacs sprouting from systemic jugular veins and/or by co-option of lymphangioblasts or hematopoietic-derived cells. It can also proceed by dedifferentiation of venous endothelial cells after their detachment from the venous system, migration to the target places within the body and assembly in the lymphatic lumen. Mechanisms of lymphatic vessel formation during embryonic development and in pathological conditions, such as tumorigenesis, wound healing, and metastasis, is regulated by a plethora of growth factors and molecules, among which the most important are VEGF-C, VEGF-D, HGF, FGF, retinoic acid, IL-3, and IL-7. Macrophages and cells bearing CD45 phenotype seem to take part in the formation of lymphatics. Macrophages might act as a source of growth factors and/or as modulators playing a role in vessel caliber regulation during lymphangiogenesis. We discuss the most important diseases of the lymphatic system, their molecular basis and tumors derived from lymphatic vessels.
在本文中，我们展示了与胚胎发育以及病理过程（如肿瘤发生、伤口愈合和其他疾病）中淋巴管形成的结构和各种方式相关的文献结果。淋巴系统的功能包括收集从循环进入组织的液体，从肠道吸收脂质和脂溶性维生素并随后进行运输，参与抗原、树突状细胞和淋巴细胞的迁移。淋巴系统也是肿瘤细胞和炎性细胞运输的途径。天然淋巴管与血管的不同之处在于其管腔不规则、基底膜不连续、缺乏周细胞，并且其内皮细胞通过由埃米林和原纤蛋白构成的微原纤维与细胞外基质有很强的锚定作用。淋巴管内皮细胞表达表面抗原，如淋巴管内皮透明质酸受体1、血小板内皮细胞黏附分子、血管内皮生长因子受体3（胎儿肝脏激酶4）和转录因子Prox-1，以及血管内皮细胞和淋巴管内皮细胞共有的分子（血小板内皮细胞黏附分子、CD34、胎儿肝脏激酶1、酪氨酸激酶受体1、酪氨酸激酶受体2、神经纤毛蛋白2）。胚胎发育过程中的淋巴管形成始于从颈总静脉萌出的淋巴囊的出现，和/或通过淋巴管母细胞或造血来源细胞的选择。它也可以通过静脉内皮细胞从静脉系统脱离后去分化、迁移到体内的目标位置并在淋巴管腔中组装来进行。胚胎发育以及病理状况（如肿瘤发生、伤口愈合和转移）期间淋巴管形成的机制受大量生长因子和分子调节，其中最重要的是血管内皮生长因子C、血管内皮生长因子D、肝细胞生长因子、成纤维细胞生长因子、视黄酸、白细胞介素-3和白细胞介素-7。巨噬细胞和具有CD45表型的细胞似乎参与了淋巴管的形成。巨噬细胞可能作为生长因子的来源和/或作为在淋巴管生成过程中调节血管管径的调节剂发挥作用。我们讨论了淋巴系统最重要的疾病、它们的分子基础以及源自淋巴管的肿瘤。
