scholarly journals Lymphatic Connexins and Pannexins in Health and Disease

2021 ◽  
Vol 22 (11) ◽  
pp. 5734
Author(s):  
Avigail Ehrlich ◽  
Filippo Molica ◽  
Aurélie Hautefort ◽  
Brenda R. Kwak
Keyword(s):  
Lymphatic System ◽  
Immune Cell ◽  
Current Knowledge ◽  
Extracellular Fluid ◽  
Cell Trafficking ◽  
Secondary Lymphedema ◽  
Transmembrane Channel ◽  
Dietary Nutrient ◽  
Lymphatic Vasculature ◽  
And Function

This review highlights current knowledge on the expression and function of connexins and pannexins, transmembrane channel proteins that play an important role in intercellular communication, in both the developing and mature lymphatic vasculature. A particular focus is given to the involvement of these proteins in functions of the healthy lymphatic system. We describe their influence on the maintenance of extracellular fluid homeostasis, immune cell trafficking to draining lymph nodes and dietary nutrient absorption by intestinal villi. Moreover, new insights into connexin mutations in primary and secondary lymphedema as well as on the implication of lymphatic connexins and pannexins in acquired cardiovascular diseases are discussed, allowing for a better understanding of the role of these proteins in pathologies linked to dysfunctions in the lymphatic system.

scholarly journals Lymphatic Clearance of Immune Cells in Cardiovascular Disease

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2594
Author(s):  
Christophe Ravaud ◽  
Nikita Ved ◽  
David G. Jackson ◽  
Joaquim Miguel Vieira ◽  
Paul R. Riley
Keyword(s):  
Immune Cells ◽  
Lymphatic System ◽  
Immune Cell ◽  
Heart Function ◽  
Cell Trafficking ◽  
Tissue Fluid ◽  
Lymphatic Endothelium ◽  
Cell Clearance ◽  
Cardiac Outcome ◽  
And Function

Recent advances in our understanding of the lymphatic system, its function, development, and role in pathophysiology have changed our views on its importance. Historically thought to be solely involved in the transport of tissue fluid, lipids, and immune cells, the lymphatic system displays great heterogeneity and plasticity and is actively involved in immune cell regulation. Interference in any of these processes can be deleterious, both at the developmental and adult level. Preclinical studies into the cardiac lymphatic system have shown that invoking lymphangiogenesis and enhancing immune cell trafficking in ischaemic hearts can reduce myocardial oedema, reduce inflammation, and improve cardiac outcome. Understanding how immune cells and the lymphatic endothelium interact is also vital to understanding how the lymphatic vascular network can be manipulated to improve immune cell clearance. In this Review, we examine the different types of immune cells involved in fibrotic repair following myocardial infarction. We also discuss the development and function of the cardiac lymphatic vasculature and how some immune cells interact with the lymphatic endothelium in the heart. Finally, we establish how promoting lymphangiogenesis is now a prime therapeutic target for reducing immune cell persistence, inflammation, and oedema to restore heart function in ischaemic heart disease.

scholarly journals Mathematical Modelling of the Structure and Function of the Lymphatic System

Mathematics ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1467
Author(s):  
Anastasia Mozokhina ◽  
Rostislav Savinkov
Keyword(s):  
Lymph Nodes ◽  
Mathematical Modelling ◽  
Mathematical Models ◽  
Lymphatic System ◽  
Current Knowledge ◽  
Structure And Function ◽  
Lymph Flow ◽  
And Function

This paper presents current knowledge about the structure and function of the lymphatic system. Mathematical models of lymph flow in the single lymphangion, the series of lymphangions, the lymph nodes, and the whole lymphatic system are considered. The main results and further perspectives are discussed.

scholarly journals Map4k4 impairs energy metabolism in endothelial cells and promotes insulin resistance in obesity

2017 ◽  
Vol 313 (3) ◽  
pp. E303-E313 ◽  
Author(s):  
Rachel J. Roth Flach ◽  
Marina T. DiStefano ◽  
Laura V. Danai ◽  
Ozlem Senol-Cosar ◽  
Joseph C. Yawe ◽  
...  
Keyword(s):  
Immune Cell ◽  
Vascular Dysfunction ◽  
Chylous Ascites ◽  
Mitogen Activated Protein Kinase ◽  
Cell Trafficking ◽  
Metabolic Dysfunction ◽  
Vascular Integrity ◽  
Adult Mice ◽  
Mitogen Activated Protein ◽  
Lymphatic Vasculature

The blood vasculature responds to insulin, influencing hemodynamic changes in the periphery, which promotes tissue nutrient and oxygen delivery and thus metabolic function. The lymphatic vasculature regulates fluid and lipid homeostasis, and impaired lymphatic function can contribute to atherosclerosis and obesity. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and lymphangiogenesis as well as atherosclerosis. Here, we show that inducible EC Map4k4 deletion in adult mice ameliorates metabolic dysfunction in obesity despite the development of chylous ascites and a concomitant striking increase in adipose tissue lymphocyte content. Despite these defects, animals lacking endothelial Map4k4 were protected from skeletal muscle microvascular rarefaction in obesity, and primary ECs lacking Map4k4 displayed reduced senescence and increased metabolic capacity. Thus endothelial Map4k4 has complex and opposing functions in the blood and lymphatic endothelium postdevelopment. Whereas blood endothelial Map4k4 promotes vascular dysfunction and impairs glucose homeostasis in adult animals, lymphatic endothelial Map4k4 is required to maintain lymphatic vascular integrity and regulate immune cell trafficking in obesity.

Non-Invasive Assessment of Lymphatic Pumping Pressure in a Rat Tail Model Utilizing Near-Infrared Imaging

2013 ◽  
Author(s):  
J. Brandon Dixon ◽  
Ryan Akin ◽  
Mike Weiler ◽  
Timothy Kassis
Keyword(s):  
Near Infrared ◽  
Infrared Imaging ◽  
Immune Cell ◽  
Vessel Diameter ◽  
Lipid Absorption ◽  
Cell Trafficking ◽  
Non Invasive ◽  
Venous Circulation ◽  
Lymphatic Vasculature ◽  
Rat Tail Model

The lymphatic vasculature consists of a network of vessels that promote unidirectional transport of fluid, proteins, and cells from the interstitium back into the blood, providing functions essential for maintaining fluid balance, immune cell trafficking, and lipid absorption from the intestine. The lymphatics generate flow through both extrinsic pumping mechanisms, such as contraction of surrounding skeletal muscle, and through the intrinsic contractility of each lymphatic vessel unit known as a lymphangion. Specialized lymphatic muscle, working in coordination with uni-directional valves separating each lymphangion, serves to contract up to 80% of the vessel diameter and drive flow from the interstitium back to the venous circulation.

Dietary and Physiological Effects of Zinc on the Immune System

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Inga Wessels ◽  
Henrike Josephine Fischer ◽  
Lothar Rink
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Immune Cell ◽  
Current Knowledge ◽  
Annual Review ◽  
Publication Date ◽  
Biological Processes ◽  
And Function ◽  
Broad Overview

Evidence for the importance of zinc for all immune cells and for mounting an efficient and balanced immune response to various environmental stressors has been accumulating in recent years. This article describes the role of zinc in fundamental biological processes and summarizes our current knowledge of zinc's effect on hematopoiesis, including differentiation into immune cell subtypes. In addition, the important role of zinc during activation and function of immune cells is detailed and associated with the specific immune responses to bacteria, parasites, and viruses. The association of zinc with autoimmune reactions and cancers as diseases with increased or decreased immune responses is also discussed. This article provides a broad overview of the manifold roles that zinc, or its deficiency, plays in physiology and during various diseases. Consequently, we discuss why zinc supplementation should be considered, especially for people at risk of deficiency. Expected final online publication date for the Annual Review of Nutrition, Volume 41 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Characterization of Near-Infrared Functional Lymphatic Imaging in the Rat Tail Model

2013 ◽  
Author(s):  
Michael Weiler ◽  
J. Brandon Dixon
Keyword(s):  
Near Infrared ◽  
Immune Cell ◽  
Imaging Modality ◽  
Lymphatic Vessels ◽  
The Body ◽  
Cell Trafficking ◽  
Nir Imaging ◽  
Lymphatic Vasculature ◽  
Rat Tail Model ◽  
Lymphatic Imaging

The lymphatic vasculature is present in nearly every tissue of the body to serve essential functions in fluid homeostasis, immune cell trafficking, and lipid transport, and it has been implicated in the progression of several diseases. Despite the critical roles that this system performs, very little is known about the lymphatic vasculature in comparison to the blood vasculature, which can be attributed, in part, to the difficulty associated with imaging lymphatic vessels. With the growing interest in studying lymphatics, near-infrared (NIR) imaging has emerged in the literature as a novel lymphatic imaging modality to simultaneously improve spatial resolution to visualize small initial lymphatics and increase temporal resolution to capture the dynamic lymphatic pump function responsible for fluid propulsion.

scholarly journals Modulation of the Vascular-Immune Environment in Metastatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 810
Author(s):  
Bo He ◽  
Ruth Ganss
Keyword(s):  
Immune Cell ◽  
Synergistic Effects ◽  
Metastatic Cancer ◽  
Resistance Mechanisms ◽  
Cell Trafficking ◽  
Primary Tumors ◽  
Adaptive Resistance ◽  
Immune Therapies ◽  
Approved Drugs ◽  
And Function

Advanced metastatic cancer is rarely curable. While immunotherapy has changed the oncological landscape profoundly, cure in metastatic disease remains the exception. Tumor blood vessels are crucial regulators of tumor perfusion, immune cell influx and metastatic dissemination. Indeed, vascular hyperpermeability is a key feature of primary tumors, the pre-metastatic niche in host tissue and overt metastases at secondary sites. Combining anti-angiogenesis and immune therapies may therefore unlock synergistic effects by inducing a stabilized vascular network permissive for effector T cell trafficking and function. However, anti-angiogenesis therapies, as currently applied, are hampered by intrinsic or adaptive resistance mechanisms at primary and distant tumor sites. In particular, heterogeneous vascular and immune environments which can arise in metastatic lesions of the same individual pose significant challenges for currently approved drugs. Thus, more consideration needs to be given to tailoring new combinations of vascular and immunotherapies, including dosage and timing regimens to specific disease microenvironments.

scholarly journals Leukocyte Trafficking via Lymphatic Vessels in Atherosclerosis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1344
Author(s):  
Kim Pin Yeo ◽  
Hwee Ying Lim ◽  
Veronique Angeli
Keyword(s):  
Immune Cell ◽  
Lymphatic Vessels ◽  
Cardiovascular Complications ◽  
Chronic Inflammatory Disease ◽  
Cell Trafficking ◽  
Functional Roles ◽  
New Findings ◽  
Lymphatic Vasculature ◽  
Acute And Chronic Inflammation ◽  
Progression Of Atherosclerosis

In recent years, lymphatic vessels have received increasing attention and our understanding of their development and functional roles in health and diseases has greatly improved. It has become clear that lymphatic vessels are critically involved in acute and chronic inflammation and its resolution by supporting the transport of immune cells, fluid, and macromolecules. As we will discuss in this review, the involvement of lymphatic vessels has been uncovered in atherosclerosis, a chronic inflammatory disease of medium- and large-sized arteries causing deadly cardiovascular complications worldwide. The progression of atherosclerosis is associated with morphological and functional alterations in lymphatic vessels draining the diseased artery. These defects in the lymphatic vasculature impact the inflammatory response in atherosclerosis by affecting immune cell trafficking, lymphoid neogenesis, and clearance of macromolecules in the arterial wall. Based on these new findings, we propose that targeting lymphatic function could be considered in conjunction with existing drugs as a treatment option for atherosclerosis.

scholarly journals Lymphatic Senescence: Current Updates and Perspectives

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 293
Author(s):  
Sebastian Lucio Filelfi ◽  
Alberto Onorato ◽  
Bianca Brix ◽  
Nandu Goswami
Keyword(s):  
Lymphatic System ◽  
Light Exposure ◽  
Contractile Activity ◽  
Lymphatic Vessels ◽  
Nerve Fibers ◽  
Treatment Modalities ◽  
Lymphatic Flow ◽  
Lymphatic Vasculature ◽  
And Function ◽  
The Impact

Lymphatic flow is necessary for maintenance of vital physiological functions in humans and animals. To carry out optimal lymphatic flow, adequate contractile activity of the lymphatic collectors is necessary. Like in all body systems, aging has also an effect on the lymphatic system. However, limited knowledge is available on how aging directly affects the lymphatic system anatomy, physiology and function. We investigated how senescence leads to alterations in morphology and function of the lymphatic vessels. We used the strategy of a review to summarize the scientific literature of studies that have been published in the area of lymphatic senescence. Searches were carried out on PubMed and Web of Science using predefined search queries. We obtained an initial set of 1060 publications. They were filtered to 114 publications based on strict inclusion and exclusion criteria. Finally, the most appropriate 57 studies that specifically addressed lymphatic senescence have been selected for the preparation of this review. Analysis of the literature showed that lymphatic senescence is associated with alterations in lymphatic muscles and nerve fibers, lymphatic glycocalyx function of lymphatic endothelial cells, effects of chronic ultraviolet light exposure and oxidative stress as well as changes in lymphatic pump, acute inflammation responses and immune function. The current review underscores the relevance of the understudied area of lymphatic senescence. Continued research on the impact of aging on the structure and function of the lymphatic vasculature is needed to provide further insights to develop innovative clinical diagnostic—and treatment—modalities as well as to reduce the morbidity associated with diseases related to the lymphatic system.

scholarly journals When form meets function: the cells and signals that shape the lymphatic vasculature during development

Development ◽  
2021 ◽  
Vol 148 (11) ◽  
Author(s):  
Mathias Francois ◽  
Anna Oszmiana ◽  
Natasha L. Harvey
Keyword(s):  
Network Formation ◽  
Immune Cell ◽  
Lymphatic Endothelial Cell ◽  
Dietary Lipids ◽  
Cell Trafficking ◽  
Tissue Fluid ◽  
Cellular Events ◽  
Formation Function ◽  
Lymphatic Vasculature ◽  
Lymphatic Network

ABSTRACT The lymphatic vasculature is an integral component of the cardiovascular system. It is essential to maintain tissue fluid homeostasis, direct immune cell trafficking and absorb dietary lipids from the digestive tract. Major advances in our understanding of the genetic and cellular events important for constructing the lymphatic vasculature during development have recently been made. These include the identification of novel sources of lymphatic endothelial progenitor cells, the recognition of lymphatic endothelial cell specialisation and heterogeneity, and discovery of novel genes and signalling pathways underpinning developmental lymphangiogenesis. Here, we review these advances and discuss how they inform our understanding of lymphatic network formation, function and dysfunction.

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