Lymph sacs

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Lymph sacs
Details
System Lymphatic system
Identifiers
Latin sacci lymphatici
TE sacs_by_E5.11.2.3.0.0.13 E5.11.2.3.0.0.13
Anatomical terminology

Lymph sacs are a part of the development of the lymphatic system, known as lymphangiogenesis. [1] The lymph sacs are precursors of the lymph vessels. [2] These sacs develop through the processes of vasculogenesis and angiogenesis. However, there is evidence of both of these processes in different organisms. In mice, it is thought that the lymphatic components form through an angiogenic process. But, there is evidence from bird embryos that gives rise to the idea that lymphatic vessels arise in the embryos through a vasculogenesis-like process from the lymphangioblastic endothelial precursor cells. [1]

The development of the lymphatic system has been a highly debated topic in developmental biology for a long time. Previously, it was debated whether the lymph sacs developed from the venous system, or if they came from spaces in the mesenchyme, which come together in a centripetal direction and secondarily opened into the veins. [3] However, more recent research has shown that the formation of the lymphatic system begins when a subset of endothelial cells from the previously formed jugular vein sprout off to form the lymphatic sacs. [4] Because lymph sacs form from the venous system, they typically contain red blood cells. [4] It is believed that the lymph sacs are directly connected to the venous system and that the venous components and lymphatic components communicate through a small hole. [4] Studies have shown that the development of lymph sacs occurs through swelling and outgrowth of pre-lymphatic clusters from the cardinal vein, in a process termed ballooning. Following ballooning, there is the process of pinching, which separates the lymph sacs from the venous system. [4]

These processes begin forming the lymph sacs during the 5th week of fetal development. At this time, the jugular lymph sacs develop. [1] These are a pair of enlargements that function in collecting fluid from the lymphatics of the upper limbs, upper trunk, head, and neck. The lymph nodes eventually develop at the place of the jugular lymphatic sacs. [1] From the left jugular lymphatic sac, the cervical part of the thoracic duct forms. From the right jugular lymphatic sac, the right lymphatic duct and the jugular and the subclavicular lymphatic trunks form. [3] One week later, during the 6th week of fetal development, four more lymph sacs form. These are the retroperitoneal lymph sac, the cysterna chyli, and paired posterior lymph sacs. [1] The posterior lymph sacs are associated with the junctions of the external and internal iliac veins. These four new lymph sacs function in the collection of lymph from the trunk and lower extremities of the body. The cysterna chyli drains into a pair of thoracic lymphatic ducts initially. [1] These ducts drain into the venous junctions of the internal jugular and subclavian veins. [1] However, these ducts eventually become one thoracic duct that is derived from the caudal portion of the right duct, the cranial portion of the left duct, and median anastomosis. [1]

There are many transcription factors that regulate the development of the lymphatic system, particularly the lymph sacs, but in all of the migrating lymphatic endothelial cell precursors, there is one specific factor present, Prospero-related homeobox-1 (PROX1). [1] Homologs of this transcription factor have been found in humans, chicks, newts, frogs, Drosophila, and zebrafish. [1] When the development of the lymphatic system begins from the cardinal vein, all of the endothelial cells appear to have the potential to become lymphatic. [1] This potential is indicated by the presence of some known lymphatic markers such as Vascular endothelial growth factor receptor-3 (Vegfr3 or Flt4; a receptor for VegfC and VegfD), and also the presence of Lyve1, which is a lymphatic specific hyluronan receptor. [1] However, regardless of the presence of these markers, it appears that only the subset of endothelial cells that begin to express Prox1 form the undeveloped lymph sacs. Once these cells start to express Prox1, they begin to express more specific lymphatic markers such as Nrp2 and Podoplanin. [1]

Many experiments involving mice have proven the importance of the Prox1 transcription factor in the development of primitive lymph sacs. [1] In experiments where Prox1 was knocked out in mice, the embryos were unable to form any lymphatic system. However, even when the mice did not have any Prox1, the endothelial cells still migrate similarly to the way they would when developing a lymphatic system, but as these cells migrate, they never develop the ability to express the more specific lymphatic markers. [1] Instead, they will begin to express markers that are specific to blood vessel endothelium. These markers include CD34 and Laminin. [1] This experiment proves that Prox1 is necessary for lymphatic cells to specify. It is believed that Prox1 is the single most important transcription factor that programs the fate of endothelial cells becoming lymphatic components. It has also been found that ectopic expression of Prox1 in blood vascular epithelium can force vascular endothelial cells to convert into lymphatic cells. [1] It has been observed that lymph nodes often develop at locations where blood vessels bifurcate, indicating that signals required for blood vessel branching might also contribute to the formation of lymph nodes. [5]

Related Research Articles

<span class="mw-page-title-main">Lymphatic system</span> Organ system in vertebrates complementary to the circulatory system

The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lymphatic tissue and lymph. Lymph is a clear fluid carried by the lymphatic vessels back to the heart for re-circulation. The Latin word for lymph, lympha, refers to the deity of fresh water, "Lympha".

<span class="mw-page-title-main">Lymph node</span> Organ of the lymphatic system

A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include B and T cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles including cancer cells, but have no detoxification function.

<span class="mw-page-title-main">Thoracic duct</span> Lymphatic vessel

In human anatomy, the thoracic duct is the larger of the two lymph ducts of the lymphatic system. The thoracic duct usually begins from the upper aspect of the cisterna chyli, passing out of the abdomen through the aortic hiatus into first the posterior mediastinum and then the superior mediastinum, extending as high up as the root of the neck before descending to drain into the systemic (blood) circulation at the venous angle.

<span class="mw-page-title-main">Lymph</span> Fluid that circulates throughout the lymphatic system

Lymph is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to be recirculated. At the origin of the fluid-return process, interstitial fluid—the fluid between the cells in all body tissues—enters the lymph capillaries. This lymphatic fluid is then transported via progressively larger lymphatic vessels through lymph nodes, where substances are removed by tissue lymphocytes and circulating lymphocytes are added to the fluid, before emptying ultimately into the right or the left subclavian vein, where it mixes with central venous blood.

<span class="mw-page-title-main">Lymphatic vessel</span> Tubular vessels that are involved in the transport of lymph and lymphocytes

The lymphatic vessels are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessels are lined by endothelial cells, and have a thin layer of smooth muscle, and adventitia that binds the lymph vessels to the surrounding tissue. Lymph vessels are devoted to the propulsion of the lymph from the lymph capillaries, which are mainly concerned with the absorption of interstitial fluid from the tissues. Lymph capillaries are slightly bigger than their counterpart capillaries of the vascular system. Lymph vessels that carry lymph to a lymph node are called afferent lymph vessels, and those that carry it from a lymph node are called efferent lymph vessels, from where the lymph may travel to another lymph node, may be returned to a vein, or may travel to a larger lymph duct. Lymph ducts drain the lymph into one of the subclavian veins and thus return it to general circulation.

<span class="mw-page-title-main">Periaortic lymph nodes</span> Human lymph nodes

The periaortic lymph nodes are a group of lymph nodes that lie in front of the lumbar vertebrae near the aorta. These lymph nodes receive drainage from the gastrointestinal tract and the abdominal organs.

<span class="mw-page-title-main">Subclavian vein</span> Blood vessel that drains the arm

The subclavian vein is a paired large vein, one on either side of the body, that is responsible for draining blood from the upper extremities, allowing this blood to return to the heart. The left subclavian vein plays a key role in the absorption of lipids, by allowing products that have been carried by lymph in the thoracic duct to enter the bloodstream. The diameter of the subclavian veins is approximately 1–2 cm, depending on the individual.

<span class="mw-page-title-main">Cisterna chyli</span> Component of the lymphoid system

The cisterna chyli or receptaculum chyli is a dilated sac at the lower end of the thoracic duct in most mammals into which lymph from the intestinal trunk and two lumbar lymphatic trunks flow. It receives fatty chyle from the intestines and thus acts as a conduit for the lipid products of digestion. It is the most common drainage trunk of most of the body's lymphatics. The cisterna chyli is a retroperitoneal structure.

<span class="mw-page-title-main">Right lymphatic duct</span> Lymphatic vessel

The right lymphatic duct is an important lymphatic vessel that drains the right upper quadrant of the human body. It forms various combinations with the right subclavian vein and right internal jugular vein.

<span class="mw-page-title-main">Jugular lymph trunk</span>

The jugular trunk is a lymphatic vessel in the neck. It is formed by vessels that emerge from the superior deep cervical lymph nodes and unite to efferents of the inferior deep cervical lymph nodes.

<span class="mw-page-title-main">Bronchomediastinal lymph trunk</span> Lymph node

The bronchomediastinal lymph trunks are essential components of the human lymphatic system, tasked with draining lymph from the tracheobronchial, internal mammary, and anterior mediastinal lymph nodes.

<span class="mw-page-title-main">C-fos-induced growth factor</span> Mammalian protein found in humans

C-fos-induced growth factor (FIGF) is a vascular endothelial growth factor that in humans is encoded by the FIGF gene.

<span class="mw-page-title-main">PROX1</span> Protein-coding gene in the species Homo sapiens

Prospero homeobox protein 1 is a protein that in humans is encoded by the PROX1 gene. The Prox1 gene is critical for the development of multiple tissues. Prox1 activity is necessary and sufficient to specify a lymphatic endothelial cell fate in endothelial progenitors located in the embryonic veins.

<span class="mw-page-title-main">Superficial lateral cervical lymph nodes</span> Group of lymph nodes in the neck

The superficial lateral cervical lymph nodes are found along the course of the external jugular vein, between the inferior aspect of the parotid gland and the supraclavicular nodes. The nodes are intercalated along the course of the vessels draining the parotid nodes and the infraauricular nodes. These nodes drain into the supraclavicular nodes, and on to the jugular trunk, followed by the thoracic duct on the left or the right lymphatic duct.

The lymphatic endothelium refers to a specialized subset of endothelial cells located in the sinus systems of draining lymph nodes. Specifically, these endothelial cells line the branched sinus systems formed by afferent lymphatic vessels, forming a single-cell layer which functions in a variety of critical physiological processes. These lymphatic endothelial cells contribute directly to immune function and response modulation, provide transport selectivity, and demonstrate orchestration of bidirectional signaling cascades. Additionally, lymphatic endothelial cells may be implicated in downstream immune cell development as well as lymphatic organogenesis. Until recently, lymphatic endothelial cells have not been characterized to their optimal potential. This system is very important in the function of continuous removal of interstitial fluid and proteins, while also having a significant function of entry for leukocytes and tumor cells. This leads to further research that is being developed on the relationship between lymphatic endothelium and metastasis of tumor cells . The lymphatic capillaries are described to be blind ended vessels, and they are made up of a single non-fenestrated layer of endothelial cells; The lymph capillaries function to aid in the uptake of fluids, macromolecules, and cells. Although they are generally similar to blood capillaries, the lymph capillaries have distinct structural differences. Lymph capillaries consist of a more wide and irregular lumen, and the endothelium in lymph capillaries is much thinner as well. Their origin has been speculated to vary based on them being dependent on specific tissue environments, and powered by organ-specific signals.(L. Gutierrez-Miranda, K. Yaniv, 2020). A lymph capillary endothelial cell is distinct from other endothelial cells in that collagen fibers are directly attached to its plasma membrane.

Lymph trunk is a collection of lymph vessels that carries lymph, and is formed by confluence of many efferent lymph vessels. It in turn drains into one of the two lymph ducts.

<span class="mw-page-title-main">Lymph duct</span>

A lymph duct is a great lymphatic vessel that empties lymph into one of the subclavian veins. There are two lymph ducts in the human body—the right lymphatic duct and the thoracic duct. The right lymphatic duct drains lymph from the right upper limb, right side of thorax and right halves of head and neck. The thoracic duct drains lymph into the circulatory system at the left brachiocephalic vein between the left subclavian and left internal jugular veins.

<span class="mw-page-title-main">Vascular remodelling in the embryo</span> Biological process

Vascular remodelling is a process which occurs when an immature heart begins contracting, pushing fluid through the early vasculature. The process typically begins at day 22, and continues to the tenth week of human embryogenesis. This first passage of fluid initiates a signal cascade and cell movement based on physical cues including shear stress and circumferential stress, which is necessary for the remodelling of the vascular network, arterial-venous identity, angiogenesis, and the regulation of genes through mechanotransduction. This embryonic process is necessary for the future stability of the mature vascular network.

Lymph node stromal cells are essential to the structure and function of the lymph node whose functions include: creating an internal tissue scaffold for the support of hematopoietic cells; the release of small molecule chemical messengers that facilitate interactions between hematopoietic cells; the facilitation of the migration of hematopoietic cells; the presentation of antigens to immune cells at the initiation of the adaptive immune system; and the homeostasis of lymphocyte numbers. Stromal cells originate from multipotent mesenchymal stem cells.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Schoenwolf, Gary C. (2009). Larsen's Human Embryology. Philadelphia, PA: Churchill Livingstone, Elsevier. pp. 425–428. ISBN   978-0443-06811-9.
  2. Dieter Marmé; Norbert Fusenig (6 December 2007). Tumor angiogenesis: basic mechanisms and cancer therapy. Springer. pp. 327–. ISBN   978-3-540-33176-6 . Retrieved 22 May 2011.
  3. 1 2 van der Putte, S.C.J. (1975). The Development of the Lymphatic System in Man. Germany: Springer-Verlag Berlin-Heidelberg. pp. 54–55. ISBN   3-540-07204-7.
  4. 1 2 3 4 Françoisa, Mathias; Kieran Shortb; Genevieve A. Seckerc; Alexander Combesa; Quenten Schwarzd; Tara-Lynne Davidsona; Ian Smythb; Young-Kwon Honge; Natasha L. Harveyc; Peter Koopmana (12 April 2012). "Segmental territories along the cardinal veins generate lymph sacs via a ballooning mechanism during embryonic lymphangiogenesis in mice". Developmental Biology. 364 (12): 89–98. doi: 10.1016/j.ydbio.2011.12.032 . PMID   22230615.
  5. Vondenhoff, Mark F.; van de Pavert, Serge A.; Dillard, Miriam E.; Greuter, Mascha; Goverse, Gera; Oliver, Guillermo; Mebius, Reina E. (2009-01-01). "Lymph sacs are not required for the initiation of lymph node formation". Development. 136 (1): 29–34. doi:10.1242/dev.028456. ISSN   1477-9129. PMC   2648609 . PMID   19060331.