Lymphangiogenesis in development and disease

2007 ◽  
Vol 98 (08) ◽  
pp. 304-310 ◽  
Author(s):  
Ruediger Liersch ◽  
Michael Detmar
Keyword(s):  
Lymph Nodes ◽  
Cancer Metastasis ◽  
Lymphatic System ◽  
Vascular System ◽  
Malignant Tumors ◽  
Inflammatory Diseases ◽  
Transplant Rejection ◽  
Lymphatic Vessels ◽  
Lipid Uptake ◽  
Molecular Control

SummaryThe lymphatic vascular system plays an important role in the maintenance of fluid homeostasis, in the afferent immune response, in the intestinal lipid uptake and in the metastatic spread of malignant cells. The recent discovery of specific markers and growth factors for lymphatic endothelium and the establishment of genetic mouse models with impairment of lymphatic function have provided novel insights into the molecular control of the lymphatic system in physiology and in embryonic development. They have also identified molecular pathways whose mutational inactivation leads to human diseases associated with lymphedema. Moreover, the lymphatic system plays a major role in chronic inflammatory diseases and in transplant rejection. Importantly, malignant tumors can directly promote lymphangiogenesis within the primary tumor and in draining lymph nodes, leading to enhanced cancer metastasis to lymph nodes and beyond. Based upon these findings, novel therapeutic strategies are currently being developed that aim at inhibiting or promoting the formation and function of lymphatic vessels in disease.

scholarly journals The lymphatic system and sentinel lymph nodes: conduit for cancer metastasis

2021 ◽  
Author(s):  
Stanley P. Leong ◽  
Alexander Pissas ◽  
Muriel Scarato ◽  
Francoise Gallon ◽  
Marie Helene Pissas ◽  
...  
Keyword(s):  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Lymph Nodes ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Lymphatic System ◽  
Early Cancer ◽  
Lymphatic Vessels ◽  
Review Article ◽  
Cancer Spread

AbstractThe lymphatic system is a complicated system consisting of the lymphatic vessels and lymph nodes draining the extracellular fluid containing cellular debris, excess water and toxins to the circulatory system. The lymph nodes serve as a filter, thus, when the lymph fluid returns to the heart, it is completely sterile. In addition, the lymphatic system includes the mucosa-associated lymphoid tissue, such as tonsils, adenoids, Peyers patches in the small bowel and even the appendix. Taking advantage of the drainage system of the lymphatics, cancer cells enter the lymphatic vessels and then the lymph nodes. In general, the lymph nodes may serve as a gateway in the majority of cases in early cancer. Occasionally, the cancer cells may enter the blood vessels. This review article emphasizes the structural integrity of the lymphatic system through which cancer cells may spread. Using melanoma and breast cancer sentinel lymph node model systems, the spread of early cancer through the lymphatic system is progressive in a majority of cases. The lymphatic systems of the internal organs are much more complicated and difficult to study. Knowledge from melanoma and breast cancer spread to the sentinel lymph node may establish the basic principles of cancer metastasis. The goal of this review article is to emphasize the complexity of the lymphatic system. To date, the molecular mechanisms of cancer spread from the cancer microenvironment to the sentinel lymph node and distant sites are still poorly understood and their elucidation should take major priority in cancer metastasis research.

scholarly journals PECULIARITIES OF CHANGES IN LYMPH COMPOSITION IN DIFFERENT FORMS OF LYMPHADENITIS MAXILLOFACIAL AREA IN CHILDREN

2019 ◽  
Vol 19 (1) ◽  
pp. 119-123
Author(s):  
P.I. Tkachenko ◽  
S.O. Bilokon ◽  
N.M. Lokhmatova ◽  
N.M. Korotych ◽  
Yu.B. Lobach
Keyword(s):  
Lymph Nodes ◽  
Oral Mucosa ◽  
Developmental Disorders ◽  
Lymphatic System ◽  
Vascular System ◽  
Lymphatic Vessels ◽  
The Body ◽  
Depth Information ◽  
Regional Lymph Nodes ◽  
Odontogenic Origin

This literature review highlights the role of the immunocompetence of the lymph substance and the oral mucosa in various clinical forms of lymphadenitis of the maxillofacial area in children. The purpose of the work was to conduct a reflective analysis of the importance of their protective responses in the development of inflammation in regional lymph nodes. According to modern conceptions about the morpho-functional significance of the lymphatic system, it is considered first of all as one of the components of the body protective system, which is anatomically closely related to the vascular system and includes capillaries, lymphatic vessels, lymph nodes, trunks and ducts through which the lymph flows from organs and systems to the site of the merge of the internal jugular and subclavian veins. In response to entering foreign particles bearing signs of alienation into the body, lymphocytes and related antibodies are being produced in the organs of the lymphatic system and then are transferred to the site of injury through the lymphatic passageways, where the immune response takes place. The presence of a significant number of nosological forms of the disease, the factors contributing to the development of acute or chronic inflammation in the lymph nodes of the face and neck can be explained by the diversity of functions performed by them and the imperfect level of the development of structural elements of the immune system in children at the general and local levels. According to the fact that the oral mucous membrane is borderline anatomical substance through which the antigenic loading is directly carried out, it is its immunocompetence that can greatly affect on the high probability of the development of inflammatory processes of odontogenic and non-odontogenic origin. The lack of in-depth information about the multifactorial mechanisms of the aetiology and pathogenesis of lymphadenitis of the maxillofacial area of different genesis in children causes poses some difficulties in their understanding, especially in children with signs of the developmental disorders in the antenatal and early postnatal periods that influences ontogenesis, thus impacting the strength of the body systemic and local immune responses. Therefore, the study of the morphological and immunohistochemical architectonics of certain sections of the oral mucosa and regional lymphatic formations including investigation of the level of their nonspecific and specific protection is an important factor in substantiating the appropriateness to include immunocorrection medicines of different pharmacological actions into the integrated therapy.

Infrared fluorescence lymphography in experimental and clinical practice

2018 ◽  
Vol 17 (2) ◽  
pp. 84-91 ◽  
Author(s):  
G. V. Papayan ◽  
A. L. Akopov ◽  
P. A. Antonyan ◽  
A. A. Ilin ◽  
N. N. Petrishchev
Keyword(s):  
Lymph Nodes ◽  
Near Infrared ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Diagnostic System ◽  
Biological Tissues ◽  
Peritumoral Injection ◽  
Intradermal Administration ◽  
Nir Fluorescence ◽  
Real Time Visualization

Introduction. Near infrared (NIR) fluorescent diagnostics is promising due to a deeper penetration into biological tissues. Material and methods. In experiments on rabbits and in clinical studies evaluation the lymphatic system with the use of the instrument complex FLUM-808 was analysed. Results. For visualization of the lymphatic vessels of the skin, the intradermal administration of ICG, dissolved in 20 % albumin in the order of 0.02 mg/ml, is optimal. Peritumoral injection of ICG allows visualizing sentinel lymph nodes in patients with lung cancer. Conclusions. The developed NIR fluorescence diagnostic system FLUM-808 allows to real time visualization of lymphatic vessels and lymph nodes.

scholarly journals Late developing cardiac lymphatic vasculature supports adult zebrafish heart function and regeneration

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Michael RM Harrison ◽  
Xidi Feng ◽  
Guqin Mo ◽  
Antonio Aguayo ◽  
Jessi Villafuerte ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Lymphatic System ◽  
Vascular System ◽  
Heart Function ◽  
Lymphatic Vessels ◽  
Adult Zebrafish ◽  
Heart Patients ◽  
Scar Size ◽  
Lymphatic Vasculature ◽  
Zebrafish Heart

The cardiac lymphatic vascular system and its potentially critical functions in heart patients have been largely underappreciated, in part due to a lack of experimentally accessible systems. We here demonstrate that cardiac lymphatic vessels develop in young adult zebrafish, using coronary arteries to guide their expansion down the ventricle. Mechanistically, we show that in cxcr4a mutants with defective coronary artery development, cardiac lymphatic vessels fail to expand onto the ventricle. In regenerating adult zebrafish hearts the lymphatic vasculature undergoes extensive lymphangiogenesis in response to a cryoinjury. A significant defect in reducing the scar size after cryoinjury is observed in zebrafish with impaired Vegfc/Vegfr3 signaling that fail to develop intact cardiac lymphatic vessels. These results suggest that the cardiac lymphatic system can influence the regenerative potential of the myocardium.

scholarly journals Single-cell mapping reveals new markers and functions of lymphatic endothelial cells in lymph nodes

2020 ◽  
Author(s):  
Noriki Fujimoto ◽  
Yuliang He ◽  
Marco D’Addio ◽  
Carlotta Tacconi ◽  
Michael Detmar ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Single Cell ◽  
Cancer Metastasis ◽  
Lymphatic Vessels ◽  
Peripheral Tolerance ◽  
Lymphatic Endothelial Cells ◽  
Subcapsular Sinus ◽  
Lymphocyte Egress

ABSTRACTLymph nodes (LNs) are highly organized secondary lymphoid organs that mediate adaptive immune responses to antigens delivered via afferent lymphatic vessels. Lymphatic endothelial cells (LECs) line intranodal lymphatic sinuses and organize lymph and antigen distribution. LECs also directly regulate T cells, mediating peripheral tolerance to self-antigens, and play a major role in many diseases including cancer metastasis. However, little is known about the phenotypic and functional heterogeneity of LN LECs. Using single-cell RNA sequencing, we comprehensively defined the transcriptome of LECs in murine skin-draining LNs, and identified new markers and functions of distinct LEC subpopulations. We found that LECs residing in the subcapsular sinus have an unanticipated function in scavenging of modified LDL and also identified a specific cortical LEC subtype implicated in rapid lymphocyte egress from LNs. Our data provide new insights into the diversity of LECs in murine lymph nodes and a rich resource for future studies into the regulation of immune responses by lymph node LECs.

Nitric Oxide Transport in Lymphatic Vessels

2011 ◽  
Author(s):  
John T. Wilson ◽  
Rebecca L. Dahlin ◽  
Olga Gasheva ◽  
David C. Zawieja ◽  
James E. Moore
Keyword(s):  
Lymph Nodes ◽  
Lymphatic System ◽  
Physiological Function ◽  
Lymphatic Vessels ◽  
Vital Role ◽  
The Body ◽  
Common Pathway ◽  
Regional Lymph Nodes ◽  
Insight Into

The lymphatic system plays a vital role in maintaining proper physiological function in the body. Its removal of proteins and other particulate matter from the tissue spaces is particularly important for the body’s prevention of extracellular edema [1]. After fluid is absorbed by the initial lymphatics, it is transported to lymph nodes where filtration occurs. In addition, the lymphatic system serves as a common pathway of initial metastases to regional lymph nodes for certain types of cancers [2]. Thus, the characterization of mass transport in the lymphatic system could lead to unprecedented insight into the treatment of such pathologies.

scholarly journals Regulation of lymphangiogenesis by extracellular vesicles in cancer metastasis

2021 ◽  
pp. 153537022110210
Author(s):  
Chu-An Wang ◽  
Shaw-Jenq Tsai
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Lymphatic Metastasis ◽  
Lymphatic Vessel ◽  
Cancer Metastasis ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Extracellular Vesicle ◽  
Tissue Fluid ◽  
Vessel Infiltration

Metastasis is not only one of the hallmarks of cancer but, unfortunately, it also is the most accurate biomarker for poor prognosis. Cancer cells metastasize through two different but eventually merged routes, the vasculature and lymphatic systems. The processes of cancer metastasis through blood vessel have been extensively studied and are well documented in the literature. In contrast, metastasis through the lymphatic system is less studied. Most people believe that cancer cells metastasize through lymphatic vessel are passive because the lymphatic system is thought to be a sewage draining system that collects whatever appears in the tissue fluid. It was recently found that cancer cells disseminated from lymphatic vessels are protected from being destroyed by our body’s defense system. Furthermore, some cancer cells or cancer-associated immune cells secrete lymphangiogenic factors to recruit lymphatic vessel infiltration to the tumor region, a process known as lymphangiogenesis. To ensure the efficiency of lymphangiogenesis, the lymphangiogenic mediators are carried or packed by nanometer-sized particles named extracellular vesicles. Extracellular vesicles are lipid bilayer particles released from eventually every single cell, including bacterium, with diameters ranging from 30 nm (exosome) to several micrometers (apoptotic body). Components carried by extracellular vesicles include but are not limited to DNA, RNA, protein, fatty acid, and other metabolites. Recent studies suggest that cancer cells not only secrete more extracellular vesicles but also upload critical mediators required for lymphatic metastasis onto extracellular vesicles. This review will summarize recent advances in cancer lymphatic metastasis and how cancer cells regulate this process via extracellular vesicle-dependent lymphangiogenesis.

Pump eflciency of lymphatic vessels: numeric estimation

2019 ◽  
Vol 34 (5) ◽  
pp. 261-268 ◽  
Author(s):  
Anastasia S. Mozokhina ◽  
Sergey I. Mukhin ◽  
Gennady I. Lobov
Keyword(s):  
Lymph Nodes ◽  
Pressure Gradient ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Lymph Flow ◽  
Dimensional Approach ◽  
One Dimensional ◽  
Numeric Estimation

Abstract A model of lymph flow in the human lymphatic system in the quasi-one-dimensional approach has been created and investigated under different conditions. The model includes an implementation of contractions and valve influence on lymph flow. We consider contractions of lymphatic vessels and their influence on resulting flow in the whole network of lymphatic vessels and lymph nodes. We have investigated flow with zero pressure gradient and have found parameters, which influence the efficiency of contractions most significantly.

scholarly journals Bacterial Lymphatic Metastasis in Infection and Immunity

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 33
Author(s):  
Matthew K. Siggins ◽  
Shiranee Sriskandan
Keyword(s):  
Lymph Nodes ◽  
Lymphatic Metastasis ◽  
Bacterial Infections ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Systemic Infection ◽  
The Body ◽  
Host Cells ◽  
Adaptive Responses ◽  
Bacterial Dissemination

Lymphatic vessels permeate tissues around the body, returning fluid from interstitial spaces back to the blood after passage through the lymph nodes, which are important sites for adaptive responses to all types of pathogens. Involvement of the lymphatics in the pathogenesis of bacterial infections is not well studied. Despite offering an obvious conduit for pathogen spread, the lymphatic system has long been regarded to bar the onward progression of most bacteria. There is little direct data on live virulent bacteria, instead understanding is largely inferred from studies investigating immune responses to viruses or antigens in lymph nodes. Recently, we have demonstrated that extracellular bacterial lymphatic metastasis of virulent strains of Streptococcus pyogenes drives systemic infection. Accordingly, it is timely to reconsider the role of lymph nodes as absolute barriers to bacterial dissemination in the lymphatics. Here, we summarise the routes and mechanisms by which an increasing variety of bacteria are acknowledged to transit through the lymphatic system, including those that do not necessarily require internalisation by host cells. We discuss the anatomy of the lymphatics and other factors that influence bacterial dissemination, as well as the consequences of underappreciated bacterial lymphatic metastasis on disease and immunity.

The lymphatic system

2017 ◽  
Author(s):  
Sinem Karaman ◽  
Aleksanteri Aspelund ◽  
Michael Detmar ◽  
Kari Alitalo
Keyword(s):  
Lymph Nodes ◽  
Vascular System ◽  
Lymphatic Vessels ◽  
Circulatory System ◽  
Dietary Fats ◽  
Venous Circulation ◽  
Tumour Metastasis ◽  
System P ◽  
Vegf Family Members ◽  
Endothelial Growth Factor

The lymphatic vascular system is an integral component of the circulatory system; it forms a one-way conduit that transports tissue interstitial components back to the venous circulation through lymph nodes. Lymphatic vessels extend to most tissues and contribute to the regulation of interstitial fluid homeostasis, trafficking of immune cells, and absorption of dietary fats from the gut. Developmentally, lymphatic vessels originate from embryonic veins and specialized angioblasts. A number of molecules have been identified in the commitment of endothelial cells to the lymphatic lineage, and the sprouting, expansion and maturation of the lymphatic vascular tree. Importantly, the vascular endothelial growth factor (VEGF) family members VEGFC and VEGFD, together with their receptors VEGFR2 and VEGFR3 have been implicated as critical regulators of lymphangiogenesis. Lymphatic vessels are involved in several human diseases, including cancer, where they contribute to tumour metastasis, the leading cause of cancer-related deaths. Lymphatic vessels regulate immune responses against foreign pathogens by transporting leucocytes to lymph nodes, but are also in involved in the regulation of self-tolerance. Defects in the lymphatic vascular system are causal for the development of lymphoedema.

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