淋巴管内皮细胞的生物学特性

淋巴管作为机体内流体动力学系统之一 ,对于维持组织液的平衡、淋巴细胞的再循环 ( Recirculation of lymphocyte)、蛋白质等大分子物质的转运 ,都具有非常重要的作用。近年来研究表明 :淋巴管内皮细胞具有活跃的代谢功能 ,能够生成和灭活多种生物活性物质。本文对近年来淋巴管内皮细胞的生物学特性研究综述如下。1　淋巴管内皮细胞的生物学特性1.1　血管紧张素的转化淋巴管内皮细胞中含有 A型血管紧张素 转移酶。血管紧张素转移酶分布于内皮细胞的表面 ,已被广泛用作内皮细胞的标志。血管紧张素 转移酶是一种羧基肽酶 ,能将十肽的血管紧…     

淋巴管新生及其在相关疾病发生和治疗中的意义

淋巴管在维持体内微环境衡定、免疫反应和肿瘤淋巴转移等方面起着重要作用,淋巴管新生与胚胎发育、外伤修复、炎症转归和肿瘤转移密切相关.在趋化因子和生长因子的作用下,淋巴管内皮细胞迁移、增殖和构成管腔,形成新的淋巴管.近年来发现淋巴管内皮祖细胞参与淋巴管新生.淋巴管内皮特异表达Prox-1、podoplanin、VEGFR-3和 LYVE-1等,这些因子和受体调控淋巴管新生.VEGF-C/VEGFR-3或VEGF-D/VEGFR-3信号途径在淋巴管新生过程中起着重要作用.VEGF-C、VEGF-D和VEGFR-3可作为基因治疗的靶点,有望治疗淋巴管新生障碍性疾病以及抗移植后免疫排斥和抗肿瘤淋巴管转移.本文主要综述了胚胎发育、先天性淋巴水肿、炎性病变和肿瘤等状态下淋巴管新生的变化及其机制、淋巴管内皮祖细胞参与淋巴管新生的过程、淋巴管内皮细胞特异性转录因子和受体对于淋巴管新生的调控作用.     

肺淋巴管平滑肌瘤病临床病理学观察

目的 探讨肺淋巴管平滑肌瘤病临床、病理特征。方法 对5例肺淋巴管平滑肌瘤病临床资料进行收集分析,HE切片观察,采用免疫组织化学(SP法)检测平滑肌肌动蛋白(SMA)、HMB45、基质金属蛋白酶(MMP)2、孕激素受体(PR)、雌激素受体(ER),并进行文献复习。结果 肺淋巴管平滑肌瘤病是原因不明的肺部疾病,只发生在女性,特别是绝经前妇女。临床表现为呼吸困难,咯血,气胸和乳糜胸等。病理学检查显示不同成熟度平滑肌细胞在细支气管壁、肺泡壁、淋巴管壁和血管壁周围增生,肺实质呈囊性变。增生的平滑肌细胞免疫组织化学5例SMA、HMB45、MMP2均阳性;1例的ER和PR均阳性,1例仅ER阳性,1例仅PR阳性,1例的ER和PR均阴性。结论 育龄期妇女如反复出现自发性气胸、咯血、活动后呼吸困难应考虑肺淋巴管平滑肌瘤病的可能,病理检查可确定肺淋巴管平滑肌瘤病的诊断。     

家兔肺内淋巴管的微细分布

目的：研究家兔肺内淋巴管的微细分布,探讨肺泡隔内是否存在淋巴管。方法：采用5′-核苷酸酶-碱性磷酸酶双重染色法(5′-Nase-ALP)、半薄切片光镜观察、超薄切片电镜观察。结果：(1)肺内淋巴管存在于富含结缔组织区,延伸至呼吸性细支气管区,不延伸至肺泡区,呼吸性细支气管外膜下可见毛细淋巴管,肺泡隔内未见毛细淋巴管和淋巴管,仅见到大量呈蓝色的毛细血管。(2)伴行肺动脉的淋巴管为肺深淋巴管系的主流,其末梢向小叶中央延伸到末级微动脉附近。(3)伴行肺静脉的淋巴管位于静脉外膜边缘的结缔组织中,与肺泡紧密相邻。结论：肺泡隔内无淋巴管,肺内淋巴管起始于呼吸性支气管。     

D-Limonene对小鼠移植瘤生长及淋巴管生成的影响

目的:观察右旋柠烯对小鼠移植瘤生长及淋巴管生成的影响,并探讨其作用机制。方法:皮下注射肉瘤(S180)腹水型瘤株构建小鼠移植瘤模型,给予D-Lim onene干预,免疫组化染色观察瘤细胞V EG F-C表达,LY V E-1标记淋巴管,观察其分布。结果:对照组瘤细胞V EG F-C表达较强,瘤周边部淋巴管较多,有淋巴结、肺转移。用药组瘤细胞V EG F-C表达较弱;瘤周边部淋巴管较少,未见淋巴结、肺转移。结论:D-Lim onene有抑制移植瘤内瘤细胞V EG F-C表达和淋巴管生成的作用,有可能降低肿瘤的淋巴道转移。     

淋巴管栓的研究进展

淋巴管栓是指栓子在淋巴管内形成,导致淋巴管回流功能受阻的病理改变。本文从淋巴管的解剖与生理功能、淋巴液的凝固过程、不同疾病继发淋巴管栓的形成机制、淋巴管栓的检测方法和治疗等五个方面综述淋巴管栓的研究进展,认为建立多种淋巴管栓模型和发明淋巴管栓的检测仪器,临床上全面观察淋巴管栓的疾病特点,优化淋巴管栓的诊治方案,实现淋巴管栓从基础研究至临床转化。     

小隐静脉旁淋巴管的应用解剖

目的　研究小隐静脉旁淋巴管的解剖特征,为临床应用提供解剖学基础。  方法　成人新鲜尸体3具,截取3对下肢。外踝后皮内注入少量双氧水,真皮下找到淋巴管,将显影剂经30G注射针注入,使其显影,追踪并显示小隐静脉旁淋巴管的走行,同时进行拍照及X线摄像,依次到达小腿及腘窝。  结果　小隐静脉旁均可见内侧支和外侧支集合淋巴管,有的始于外踝后区真皮下,有的始于小腿后下部。淋巴管沿小隐静脉两侧蜿蜒曲折向心性走行,管间有分支相连接。近腘窝时,淋巴管与小隐静脉一起穿过深筋膜进入腘窝,然后发出多个小分支汇入淋巴结。此组淋巴管管径在0.3~1.5 mm之间,近侧较粗,远侧稍细。  结论　精确描述了下肢小隐静脉旁淋巴管的分布与走行,为临床应用提供重要的解剖学参考。     

淋巴管系统与肿瘤新生淋巴管研究方法新进展

长期以来 ,由于缺乏特异的淋巴管系统研究方法与标记技术 ,淋巴管的研究报道较少。新研制的较特异敏感的染色方法以及新近发现的多种淋巴管内皮细胞标记物 ,将深化对淋巴管系统结构功能的认识和肿瘤新生淋巴管在淋巴道转移过程中的作用机制研究     

小鼠恶性黑色素移植瘤模型的建立及其淋巴管内皮细胞透明质酸受体1的表达

目的:建立小鼠皮肤恶性黑色素移植瘤模型,探讨小鼠皮肤恶性黑色素移植瘤组织内淋巴管的生成情况。方法:体外培养B16瘤细胞,接种B16瘤细胞于C57BL/6小鼠右侧背部皮内,构建C57BL/6小鼠皮肤恶性黑色素移植瘤模型;应用H-E染色、淋巴管内皮细胞透明质酸受体1(1ymphatic vessel endothelial hyaluronan receptor-1, LYVE-1)免疫组化染色确认模型和观察肿瘤组织内淋巴管的生成情况。结果:建立了恶性黑色素移植瘤模型;LY- VE-1主要着色于正常组织和移植瘤组织中淋巴管内皮细胞的细胞膜上;恶性黑色素瘤组织中淋巴管密度明显高于正常皮肤组织。结论:构建C57BL/6小鼠皮肤恶性黑色素移植瘤模型是获得恶性黑色素瘤组织和进一步研究的有效手段;LYVE-1是特异性较高的淋巴管内皮标记物;小鼠皮肤恶性黑色素移植瘤组织中可能存在淋巴管的新生。     

大隐静脉旁淋巴管的应用解剖

目的　研究大隐静脉周围淋巴管的解剖学特征,为治疗下肢继发性阻塞性淋巴水肿提供解剖学基础。  方法　择成年新鲜尸体3具,截取3对下肢。在内踝后皮内,注入少量双氧水,于真皮下找到淋巴管,将显影剂经30G注射针注入淋巴管。在下肢内侧沿显影之淋巴管进行追踪解剖、照像及X线记录。  结果　从内踝后区至腹股沟可见不同数量、大小的淋巴管,呈向心性、蜿蜒起伏地与大隐静脉伴行于下肢内侧的皮下组织内。管径在0.2 ~1.8 mm之间。在行程中淋巴管分叉或合流、或与附近淋巴管交叉通过。汇入腹股沟淋巴结前分成许多小分支。解剖过程中,发现了淋巴管壁的营养血管。  结论　详细描叙了从内踝后区到腹股沟淋巴结的淋巴通路。为治疗继发性淋巴水肿和其他与下肢淋巴系有关的疾病时提供形态学基础。     

Pleural function and lymphatics

The pleural space plays an important role in respiratory function as the negative intrapleural pressure regimen ensures lung expansion and in the mean time maintains the tight mechanical coupling between the lung and the chest wall. The efficiency of the lung–chest wall coupling depends upon pleural liquid volume, which in turn reflects the balance between the filtration of fluid into and its egress out of the cavity. While filtration occurs through a single mechanism passively driving fluid from the interstitium of the parietal pleura into the cavity, several mechanisms may co‐operate to remove pleural fluid. Among these, the pleural lymphatic system emerges as the most important one in quantitative terms and the only one able to cope with variable pleural fluid volume and drainage requirements. In this review, we present a detailed account of the actual knowledge on: (a) the complex morphology of the pleural lymphatic system, (b) the mechanism supporting pleural lymph formation and propulsion, (c) the dependence of pleural lymphatic function upon local tissue mechanics and (d) the effect of lymphatic inefficiency in the development of clinically severe pleural and, more in general, respiratory pathologies.     

肺内液黏度和表面张力测量的临床意义与测量方法

肺内液主要指由气道黏液和肺泡内表面衬里液所形成的一连续液体薄层,对于维持肺的健康至关重要。介绍肺内液流变学特性在维持气道稳定性、保证肺正常的屏障与清除功能、避免呼吸机相关性肺损伤和新生儿呼吸窘迫综合征表面活性剂替代治疗等方面的临床意义,同时总结Langmuir-Wilhelmy天平法、捕获气泡法、毛细管黏度计和旋转黏度计等液体表面张力和黏度测量的经典方法,以及粒子追踪微流变仪、轴对称液滴边缘形状分析等新技术,比较这些方法的优缺点,为临床研究肺内液流变学特性辅助肺疾病的诊断和治疗提供重要参考。     

Morphometric analysis of intralobular, interlobular and pleural lymphatics in normal human lung

In spite of their presumed relevance in maintaining interalveolar septal fluid homeostasis, the knowledge of the anatomy of human lung lymphatics is still incomplete. The recent discovery of reliable markers specific for lymphatic endothelium has led to the observation that, contrary to previous assumptions, human lymphatic vessels extend deep inside the pulmonary lobule in association with bronchioles, intralobular arterioles or small pulmonary veins. The aim of this study was to provide a morphometric characterization of lymphatic vessels in the periphery of the human lung. Human lung sections were immunolabelled with the lymphatic marker D2-40, followed by blood vessel staining with von Willebrand Factor. Lymphatic vessels were classified into: intralobular (including those associated with bronchovascular bundles, perivascular, peribronchiolar and interalveolar), pleural (in the connective tissue of the visceral pleura), and interlobular (in interlobular septa). The percentage area occupied by the lymphatic lumen was much greater in the interlobular septa and in the subpleural space than in the lobule. Most of the intralobular lymphatic vessels were in close contact with a blood vessel, either alone or within a bronchovascular bundle, whereas 7% were associated with a bronchiole and < 1% were not connected to blood vessels or bronchioles (interalveolar). Intralobular lymphatic size progressively decreased from bronchovascular through to peribronchiolar, perivascular and interalveolar lymphatics. Lymphatics associated with bronchovascular bundles had similar morphometric characteristics to pleural and interlobular lymphatics. Shape factors were similar across lymphatic populations, except that peribronchiolar lymphatics had a marginally increased roundness and circularity, suggesting a more regular shape due to increased filling, and interlobular lymphatics had greater elongation, due to a greater proportion of conducting lymphatics cut longitudinally. Unsupervised cluster analysis confirmed a marked heterogeneity of lymphatic vessels both within and between groups, with a cluster of smaller vessels specifically represented in perivascular and interalveolar lymphatics within the alveolar interstitium. Our data indicate that intralobular lymphatics are a heterogeneous population, including vessels surrounding the bronchovascular bundle analogous to the conducting vessels present in the pleural and interlobular septa, many small perivascular lymphatics responsible for maintaining fluid balance in the alveolar interstitium, and a minority of intermediate lymphatics draining the peripheral airways. These lymphatic populations could be differentially involved in the pathogenesis of diseases preferentially involving distinct lung compartments.     

Pulmonary lymphatic filling is increased in spontaneously hypertensive rats

Extravascular lung liquid must rely on tissue-space pressure gradients to drive it into the lymphatics because the fluid is outside the lymphatic contractile pumping and valve control. Focal tissue pressure changes could result from muscular contraction in the blood vessel walls. Perivascular lymphatics usually lie within the adventitia of pulmonary blood vessels, and are generally more noticeable in veins than arteries. Spontaneously hypertensive rats have exaggerated focal pulmonary venous muscle (venous sphincters). These muscular tufts are often near initial lymphatics; if their contraction was important for lymph transport, spontaneously hypertensive rats could have more lymphatic filling in the areas of the pulmonary venous sphincters than normotensive rats. Because the focal muscularity is found in pulmonary veins more than arteries, veins may have more focal lymphatic filling than arteries. To test these hypotheses, lung histology and vascular and lymphatic casts of spontaneously hypertensive and normotensive rats were examined. Contracted venous sphincters were found on 108 of 127 veins with lymphatics in the spontaneously hypertensive rats and 5 of 41 in the normotensive rats P<0.01). The spontaneously hypertensive rats had deeper venous contractions and more lymphatic filling around both arteries and veins (P<0.01). In the hypertensive rats, the venous was greater than the arterial lymphatic filling (P<0.01). On the pleural surface, hypertensive rats also had greater lymphatic filling than controls (P<0.01). This anatomic evidence suggests that pulmonary venous sphincters are associated with focal lymphatic filling, and perivascular muscle action might be a component of the pulmonary lymphatic system.     

Effect of extracellular fluid volume expansion on the interparabronchial septum of the avian lung

Scanning electron microscopy was used to examine the interparabronchial septa of chickens as a potential site of lymphatic drainage in the avian lung. Anaesthetized chickens were subjected to extracellular fluid volume expansion to produce pulmonary oedema as a result of increased capillary fluid flux into the interstitial spaces of the lung. In normal (control) chickens, the adjacent parabronchi were separated by a minimal septal space. In the "volume-loaded" birds, however, the interparabronchial septal spaces were measurably thickened and engorged as a result of hydrostatic pulmonary oedema. These results, which were consistent with reports of the effect of hydrostatic pulmonary oedema in mammals, suggest that the interparabronchial septum is a potential route of lymphatic drainage in the avian lung.     

Organization and developmental aspects of lymphatic vessels

The lymphatic system plays important roles in maintaining tissue fluid homeostasis, immune surveillance of the body, and the taking up dietary fat and fat-soluble vitamins A, D, E and K. The lymphatic system is involved in many pathological conditions, including lymphedema, inflammatory diseases, and tumor dissemination. A clear understanding of the organization of the lymphatic vessels in normal conditions would be critically important to develop new treatments for diseases involving the lymphatic vascular system. Therefore, the present paper reviews the organization of the lymphatic vascular system of a variety of organs, including the thyroid gland, lung and pleura, small intestine, cecum and colon in the rat, the diaphragm in the rat, monkey, and human, Peyer's patches and the appendix in the rabbit, and human tonsils. Methods employed include scanning electron microscopy of lymphatic corrosion casts and tissues with or without treatment of alkali maceration technique, transmission electron microscopy of intact tissues, confocal microscopy in conjunction with immunohistochemistry to some lymphatic-specific markers (i.e., LYVE-1 and VEGFR-3), and light microscopy in conjunction with enzyme-histochemistry to 5'-nucleotidase. Some developmental aspects of the lymphatic vessels and lymphedema are also discussed.     

Lung lymphatic anatomy and correlates

The pulmonary lymphatics do much more than keep the lung dry. They defend the lungs from airborne particles and microbes and allow a local influx of liquid to clear and clean inflamed or damaged tissue. Lymphatic morphology, especially the three-dimensional structure, is best demonstrated by casting the lymphatics, corroding the tissue, and viewing the casts by scanning electron microscopy. With this technique, different lymphatic forms exist. On the pleural surface prelymphatics are simply tissue planes that connect with lymphatic channels. Reservoir lymphatics are another form of initial lymphatics that have blind-ending pouches. They empty into conduit lymphatics. Lymphatics around blood vessels and airways are generally tubular and saccular. In the last decade, lymphatic markers have been discovered that allow the study of lymphatic development in health and disease. Modulators of these pathways could be potential therapeutics for diverse pulmonary problems such as cancer and lung transplantation. The size of the lymphatic system expands manifold in response to an excess fluid load, cancer, or inflammation. Immune cells move through the lymphatics, mature, and become activated there. The lymphatics enable the immune defense system by allowing a sequestered place and close proximity for antigen presentation and lymphocyte maturation.     

Pulmonary lymphatics and their spatial relationship to venous sphincters

Background: Pulmonary lymphatics are critical to clearing lung fluid. Although their structure can be shown with light and transmission electron microscopy, scanning electron microscopy of their casts can better show their number, size, shape, distribution, and degree of filling. This technique has identified four forms of lung lymphatics, but these forms have not been fully evaluated by tissue microscopy. A most important site of pulmonary edema formation, the pulmonary capillary, is just upstream from small veins which have focal, smooth muscle tufts termed venous sphincters. Because of their constricting potential, these sphincters may control lung perfusion and cause edema. Methods: With light and transmission electron microscopy of tissue and scanning electron microscopy of casts, the lymphatic forms were explored in relation to the tissue anatomy in rats without pulmonary edema and with mild-to-moderate edema caused by extended vascular rinsing. Results: The edematous lungs had increased sacculo-tubular lymphatics adjacent to the venous sphincters. These lymphatics were in the adventitial connective tissue and were partially endothelialized. As lymphatics became more tubular their endothelium became more complete. Collagen fibers traversed the lumen of these lymphatics even where endothelial cells were present and caused the lines on the surface of the lymphatic casts. Overlapping endothelial cells caused clefts on the casts. Conclusions: Scanning electron microscopy of lymphatic casts better defines their ultrastructure and shows the spatial relationship of veins and their sphincters to venous lymphatics. Sphincter contraction may influence pulmonary lymph production which could affect other aspects of regional lung perfusion. © 1995 Wiley-Liss, Inc.     

Role of nitric oxide in the pathogenesis of chronic pulmonary hypertension

Chronic pulmonary hypertension is a serious complication of a number of chronic lung and heart diseases. In addition to vasoconstriction, its pathogenesis includes injury to the peripheral pulmonary arteries leading to their structural remodeling. Increased pulmonary vascular synthesis of an endogenous vasodilator, nitric oxide (NO), opposes excessive increases of intravascular pressure during acute pulmonary vasoconstriction and chronic pulmonary hypertension, although evidence for reduced NO activity in pulmonary hypertension has also been presented. NO can modulate the degree of vascular injury and subsequent fibroproduction, which both underlie the development of chronic pulmonary hypertension. On one hand, NO can interrupt vascular wall injury by oxygen radicals produced in increased amounts in pulmonary hypertension. NO can also inhibit pulmonary vascular smooth muscle and fibroblast proliferative response to the injury. On the other hand, NO may combine with oxygen radicals to yield peroxynitrite and other related, highly reactive compounds. The oxidants formed in this manner may exert cytotoxic and collagenolytic effects and, therefore, promote the process of reparative vascular remodeling. The balance between the protective and adverse effects of NO is determined by the relative amounts of NO and reactive oxygen species. We speculate that this balance may be shifted toward more severe injury especially during exacerbations of chronic diseases associated with pulmonary hypertension. Targeting these adverse effects of NO-derived radicals on vascular structure represents a potential novel therapeutic approach to pulmonary hypertension in chronic lung diseases.     

Biofluid Mechanics of Special Organs and the Issue of System Control

In the field of fluid flow within the human body, focus has been placed on the transportation of blood in the systemic circulation since the discovery of that system; but, other fluids and fluid flow phenomena pervade the body. Some of the most fascinating fluid flow phenomena within the human body involve fluids other than blood and a service other than transport—the lymphatic and pulmonary systems are two striking examples. While transport is still involved in both cases, this is not the only service which they provide and blood is not the only fluid involved. In both systems, filtration, extraction, enrichment, and in general some “treatment” of the fluid itself is the primary function. The study of the systemic circulation has also been conventionally limited to treating the system as if it were an open-loop system governed by the laws of fluid mechanics alone, independent of physiological controls and regulations. This implies that system failures can be explained fully in terms of the laws of fluid mechanics, which of course is not the case. In this paper we examine the clinical implications of these issues and of the special biofluid mechanics issues involved in the lymphatic and pulmonary systems.