Calcium Regulation in Lymphatic Endothelial Cells Under Flow

Author(s):  
Mohammad Jafarnejad ◽  
Walter E. Cromer ◽  
Roland R. Kaunas ◽  
David C. Zawieja ◽  
James E. Moore

The lymphatic system collects interstitial fluid and proteins and pumps them back to the blood circulatory system. Additionally, it is important in lipid uptake in the mesentery and immune response. Any failure of the system in pumping lymph results in swelling of tissue and/or organ(s), or lymphedema. The lymphatic system consists of initial lymphatic capillaries and larger collecting vessels. The latter contain tubular regions covered with contracting lymphatic muscle cells, which are separated by bi-leaflet valves to ensure unidirectional flow [1].

2002 ◽  
Vol 82 (3) ◽  
pp. 673-700 ◽  
Author(s):  
Lotta Jussila ◽  
Kari Alitalo

Blood and lymphatic vessels develop in a parallel, but independent manner, and together form the circulatory system allowing the passage of fluid and delivering molecules within the body. Although the lymphatic vessels were discovered already 300 years ago, at the same time as the blood circulation was described, the lymphatic system has remained relatively neglected until recently. This is in part due to the difficulties in recognizing these vessels in tissues because of a lack of specific markers. Over the past few years, several molecules expressed specifically in the lymphatic endothelial cells have been characterized, and knowledge about the lymphatic system has started to accumulate again. The vascular endothelial growth factor (VEGF) family of growth factors and receptors is involved in the development and growth of the vascular endothelial system. Two of its family members, VEGF-C and VEGF-D, regulate the lymphatic endothelial cells via their receptor VEGFR-3. With the aid of these molecules, lymphatic endothelial cells can be isolated and cultured, allowing detailed studies of the molecular properties of these cells. Also the role of the lymphatic endothelium in immune responses and certain pathological conditions can be studied in more detail, as the blood and lymphatic vessels seem to be involved in many diseases in a coordinated manner. Discoveries made so far will be helpful in the diagnosis of certain vascular tumors, in the design of specific treatments for lymphedema, and in the prevention of metastatic tumor spread via the lymphatic system.


Author(s):  
David DeRoche ◽  
Zachary Sharp

Lymphedema is a medical condition caused by an excess of fluid collecting in the interstitial tissue. When the lymphatic system is functioning normally, the interstitial fluid passes into the lymphatic capillaries, thought the lymphatic ducts, and returns to the circulatory system [1]. If this system is disrupted due to congenital reasons, surgery, or radiation therapy associated with cancer treatment, the fluid is unable to properly drain [2]. This collection of fluid leads to swelling of the affected area, usually the legs or arms (Figure 1).


2021 ◽  
Vol 22 (9) ◽  
pp. 4458
Author(s):  
Louise A. Johnson

The lymphatic system plays crucial roles in immunity far beyond those of simply providing conduits for leukocytes and antigens in lymph fluid. Endothelial cells within this vasculature are distinct and highly specialized to perform roles based upon their location. Afferent lymphatic capillaries have unique intercellular junctions for efficient uptake of fluid and macromolecules, while expressing chemotactic and adhesion molecules that permit selective trafficking of specific immune cell subsets. Moreover, in response to events within peripheral tissue such as inflammation or infection, soluble factors from lymphatic endothelial cells exert “remote control” to modulate leukocyte migration across high endothelial venules from the blood to lymph nodes draining the tissue. These immune hubs are highly organized and perfectly arrayed to survey antigens from peripheral tissue while optimizing encounters between antigen-presenting cells and cognate lymphocytes. Furthermore, subsets of lymphatic endothelial cells exhibit differences in gene expression relating to specific functions and locality within the lymph node, facilitating both innate and acquired immune responses through antigen presentation, lymph node remodeling and regulation of leukocyte entry and exit. This review details the immune cell subsets in afferent and efferent lymph, and explores the mechanisms by which endothelial cells of the lymphatic system regulate such trafficking, for immune surveillance and tolerance during steady-state conditions, and in response to infection, acute and chronic inflammation, and subsequent resolution.


2019 ◽  
Vol 18 (1) ◽  
pp. 104-112 ◽  
Author(s):  
G. I. Lobov

Accomplishments in the identifcation of lymphatic endothelial cells and the ability to differentiate them from the endothelial cells of blood vessels have contributed to progress in recent decades in studying the role of the lymphatic system in the body. Preclinical and clinical studies of the last decade have shown that changes in the lymphatic vascular network are observed in almost all lung diseases. At the same time, it remains unclear whether the lymphatic vessels and lung nodes are being part of the overall process of lung remodeling or they make a defnite contribution to the pathogenesis of diseases of the respiratory system. This review presents current data on the morphology and physiology of lymphatic vessels and nodes, their role in the regulation of interstitial fluid homeostasis, lipid transportation and immune responses as well as describes the mechanisms of regulation of the transport function of lymphatic vessels. Data on the role of the lymphatic system of the lungs in the exchange of fluid in the interstitial space of the lungs are presented in the review. The results of studies of the last two decades on the formation and reabsorption of pleural fluid and the role of various lymphatic networks in regulating its volume are described. Finally, modern ideas on the mechanisms of pulmonary edema are outlined and important questions of the lymphatic biology of the respiratory system are identifed, still remaining unanswered today.


2021 ◽  
Vol 22 (21) ◽  
pp. 11976
Author(s):  
Hannah den Braanker ◽  
Astrid C. van Stigt ◽  
Marc R. Kok ◽  
Erik Lubberts ◽  
Radjesh J. Bisoendial

Lymphatic endothelial cells (LECs) line the lymphatic vasculature and play a central role in the immune response. LECs have abilities to regulate immune transport, to promote immune cell survival, and to cross present antigens to dendritic cells. Single-cell RNA sequencing (scRNA) technology has accelerated new discoveries in the field of lymphatic vascular biology. This review will summarize these new findings in regard to embryonic development, LEC heterogeneity with associated functional diversity, and interactions with other cells. Depending on the organ, location in the lymphatic vascular tree, and micro-environmental conditions, LECs feature unique properties and tasks. Furthermore, adjacent stromal cells need the support of LECs for fulfilling their tasks in the immune response, such as immune cell transport and antigen presentation. Although aberrant lymphatic vasculature has been observed in a number of chronic inflammatory diseases, the knowledge on LEC heterogeneity and functional diversity in these diseases is limited. Combining scRNA sequencing data with imaging and more in-depth functional experiments will advance our knowledge of LECs in health and disease. Building the case, the LEC could be put forward as a new therapeutic target in chronic inflammatory diseases, counterweighting the current immune-cell focused therapies.


1976 ◽  
Vol 68 (1) ◽  
pp. 163-167 ◽  
Author(s):  
JM Lauweryns ◽  
J Baert ◽  
W De-Loecker

Several and various types of cells contain fine cytoplasmic filaments closely resembling the myofilaments of muscle cells (2, 18, 23, 24). In many of these cells and especially when cultured, it has been demonstrated that some of these filaments react with heavy meromyosin (HMM) in the same way as do the actin filaments of muscle cells (3, 6 7). This suggests that these filaments may be actinoid and form part of a contractile system. As fine intracytoplasmic filaments do occur in lymphatic endothelial cells (2, 14), we undertook an electron microscope investigation of their fine structure and their reaction on incubation with HMM and EDTA. We postulated that lymphatic endothelial cells possess a contractile filamentous system to which these filaments belong.


2021 ◽  
Vol 22 (4) ◽  
pp. 2086
Author(s):  
Seita Morishita ◽  
Takaki Sato ◽  
Shou Oosuka ◽  
Taeko Horie ◽  
Teruyo Kida ◽  
...  

We previously reported that the bursa premacularis (BPM), a peculiar vitreous structure located above the macula, contains numerous cells expressing markers of lymphatic endothelial cells, such as podoplanin and LYVE-1. Herein, we examined the expression of lymphatic markers in the Berger’s space (BS), BPM, and vitreous core (VC). BS, BPM, and VC specimens were selectively collected in macular hole and epiretinal membrane patients during vitrectomy and were then immunostained with antibodies for podoplanin, LYVE-1, and fibrillin-1 and -2. By visualization using triamcinolone acetonide, the BS was recognized as a sac-like structure with a septum located behind the lens as well as BPM. Those tissues adhered to the lens or retina in a circular manner by means of a ligament-like structure. Immunostaining showed intense expression of podoplanin and LYVE-1 in the BS. Both BS and BPM stained strongly positive for fibrillin-1 and -2. The VC was faintly stained with antibodies for those lymph-node markers. Our findings indicate that both BS and BPM possibly belong to the lymphatic system, such as lymph nodes, draining excess fluid and waste products into lymphatic vessels in the dura mater of the optic nerve and the ciliary body, respectively, via intravitreal canals.


2000 ◽  
Vol 37 (1) ◽  
pp. 85-95 ◽  
Author(s):  
E Sinzelle ◽  
J P Duong Van Huyen ◽  
S Breiteneder-Geleff ◽  
E Braunberger ◽  
A Deloche ◽  
...  

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