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Lymphatic Research and Biology 2009The lymphatic system has important roles in body fluid regulation, macromolecular homeostasis, lipid absorption, and immune function. To accomplish these roles,...
The lymphatic system has important roles in body fluid regulation, macromolecular homeostasis, lipid absorption, and immune function. To accomplish these roles, lymphatics must move fluid and its other contents (macromolecules, lipids/chylomicra, immune cells) from the interstitium through the lymphatics, across the nodes, and into the great veins. Thus, the principal task of the lymphatic vascular system is transport. The body must impart energy to the lymph via pumping mechanisms to propel it along the lymphatic network and use pumps and valves to generate lymph flow and prevent its backflow. The lymphatic system utilizes both extrinsic pumps, which rely on the cyclical compression and expansion of lymphatics by surrounding tissue forces, and intrinsic pumps, which rely on the intrinsic rapid/phasic contractions of lymphatic muscle. The intrinsic lymph pump function can be modulated by neural, humoral, and physical factors. Generally, increased lymph pressure/stretch of the muscular lymphatics activates the intrinsic lymph pump, while increased lymph flow/shear in the muscular lymphatics can either activate or inhibit the intrinsic lymph pump depending on the pattern and magnitude of the flow. To regulate lymph transport, lymphatic pumping and resistance must be controlled. A better understanding of these mechanisms could provide the basis for the development of better diagnostic and treatment modalities for lymphatic dysfunction.
Topics: Animals; Humans; Lymph; Lymphatic System; Muscle Contraction
PubMed: 19534632
DOI: 10.1089/lrb.2009.0007 -
Anatomical Record (Hoboken, N.J. : 2007) Jun 2008The liver produces a large amount of lymph, which is estimated to be 25 to 50 % of lymph flowing through the thoracic duct. The hepatic lymphatic system falls into three... (Review)
Review
The liver produces a large amount of lymph, which is estimated to be 25 to 50 % of lymph flowing through the thoracic duct. The hepatic lymphatic system falls into three categories depending on their locations: portal, sublobular, and superficial lymphatic vessels. It is suggested that 80 % or more of hepatic lymph drains into portal lymphatic vessels, while the remainder drains through sublobular and capsular lymphatic vessels. The hepatic lymph primarily comes from the hepatic sinusoids. Our tracer studies, together with electron microscopy, show many channels with collagen fibers traversing through the limiting plate and connecting the space of Disse with the interstitial space either in the portal tracts, or around the sublobular veins. Fluid filtered out of the sinusoids into the space of Disse flows through the channels traversing the limiting plate either independently of blood vessels or along blood vessels and enters the interstitial space of either portal tract or sublobular veins. Fluid in the space of Disse also flows through similar channels traversing the hepatocytes intervening between the space of Disse and the hepatic capsule and drains into the interstitial space of the capsule. Fluid and migrating cells in the interstitial space pass through prelymphatic vessels to finally enter the lymphatic vessels. The area of the portal lymphatic vessels increases in liver fibrosis and cirrhosis and in idiopathic portal hypertension. Lymphatic vessels are abundant in the immediate vicinity of the hepatocellular carcinoma (HCC) and liver metastasis. HCCs expressing vascular endothelial growth factor-C are more liable to metastasize, indicating that lymphangiogenesis is associated with their enhanced metastasis.
Topics: Animals; Blood Cells; Blood Vessels; Cell Movement; Corrosion Casting; Humans; Liver; Liver Diseases; Lymph; Lymphatic Vessels; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Rabbits; Rats
PubMed: 18484610
DOI: 10.1002/ar.20681 -
Wiley Interdisciplinary Reviews.... 2013The lymphatic vasculature plays vital roles in tissue fluid balance, immune defense, metabolism, and cancer metastasis. In adults, lymphatic vessel formation and... (Review)
Review
The lymphatic vasculature plays vital roles in tissue fluid balance, immune defense, metabolism, and cancer metastasis. In adults, lymphatic vessel formation and remodeling occur primarily during inflammation, development of the corpus luteum, wound healing, and tumor growth. Unlike the blood circulation, where unidirectional flow is sustained by the pumping actions of the heart, pumping actions intrinsic to the lymphatic vessels themselves are important drivers of lymphatic flow. This review summarizes critical components that control lymphatic physiology.
Topics: Animals; Humans; Lymph; Lymphatic Diseases; Lymphatic Vessels; Models, Biological
PubMed: 23209022
DOI: 10.1002/wsbm.1201 -
JCI Insight Apr 2018Mucosal-associated invariant T cells (MAIT cells) recognize bacterial metabolites as antigen and are found in blood and tissues, where they are poised to contribute to...
Mucosal-associated invariant T cells (MAIT cells) recognize bacterial metabolites as antigen and are found in blood and tissues, where they are poised to contribute to barrier immunity. Recent data demonstrate that MAIT cells located in mucosal barrier tissues are functionally distinct from their blood counterparts, but the relationship and circulation of MAIT cells between blood and different tissue compartments remains poorly understood. Previous studies raised the possibility that MAIT cells do not leave tissue and may either be retained or undergo apoptosis. To directly address if human MAIT cells exit tissues, we collected human donor-matched thoracic duct lymph and blood and analyzed MAIT cell phenotype, transcriptome, and T cell receptor (TCR) diversity by flow cytometry and RNA sequencing. We found that MAIT cells were present in the lymph, despite being largely CCR7- in the blood, thus indicating that MAIT cells in the lymph migrated from tissues and were capable of exiting tissues to recirculate. Importantly, MAIT cells in the lymph and blood had highly overlapping clonotype usage but distinct transcriptome signatures, indicative of differential activation states.
Topics: Adolescent; Adult; Aged; Cell Separation; Child; Child, Preschool; Flow Cytometry; Gene Expression Profiling; Humans; Immunity, Mucosal; Lymph; Middle Aged; Mucosal-Associated Invariant T Cells; Mucous Membrane; Receptors, Antigen, T-Cell; Thoracic Duct; Young Adult
PubMed: 29618662
DOI: 10.1172/jci.insight.98487 -
Glucose and GLP-2 (Glucagon-Like Peptide-2) Mobilize Intestinal Triglyceride by Distinct Mechanisms.Arteriosclerosis, Thrombosis, and... Aug 2019Dietary triglycerides are partially retained in the intestine within intracellular or extracellular compartments, which can be rapidly mobilized in response to several...
OBJECTIVE
Dietary triglycerides are partially retained in the intestine within intracellular or extracellular compartments, which can be rapidly mobilized in response to several stimuli, including glucose and GLP-2 (glucagon-like peptide-2). To elucidate the mechanism of intestinal lipid mobilization, this study examined the patterns and time course of lymph flow and triglycerides after glucose and GLP-2 treatment in rats. Approach and Results: Lymph flow, triglyceride concentration, and triglyceride output were assessed in mesenteric lymph duct-cannulated rats in response to an intraduodenal (i.d.) lipid bolus followed 5 hours later by either (1) i.d. saline+intraperitoneal (i.p.) saline (placebo), (2) i.d. glucose plus i.p. saline, (3) i.d. saline+i.p. GLP-2, or (4) i.d. glucose+i.p. GLP-2. GLP-2 and glucose administered alone or in combination stimulated total triglyceride output to a similar extent, but the timing and pattern of stimulation differed markedly. Whereas GLP-2 rapidly increased lymph flow with no effect on lymph triglyceride concentration or triglyceride:apoB48 (apolipoprotein B48) ratio (a surrogate marker of chylomicron size) compared with placebo, glucose transiently decreased lymph flow followed by delayed stimulation of lymph flow and increased lymph triglyceride concentration and triglyceride:apoB48 ratio.
CONCLUSIONS
Glucose and GLP-2 robustly enhanced intestinal triglyceride output in rats but with different effects on lymph flow, lymph triglyceride concentration, and chylomicron size. GLP-2 stimulated triglyceride output primarily by enhancing lymph flow with no effect on chylomicron size, whereas glucose mobilized intestinal triglycerides, stimulating secretion of larger chylomicrons. This suggests that these 2 stimuli mobilize intestinal lipid by different mechanisms.
Topics: Animals; Apolipoprotein B-48; Chylomicrons; Glucagon-Like Peptide 2; Glucose; Intestinal Mucosa; Lymph; Male; Rats; Rats, Sprague-Dawley; Triglycerides
PubMed: 31294621
DOI: 10.1161/ATVBAHA.119.313011 -
The Journal of Physiology Dec 19731. Three lymphatic beds have been found in the rabbit hind limb:(i) the lymph from the foot and ankle drains into lymphatics which run with the deep veins to the...
1. Three lymphatic beds have been found in the rabbit hind limb:(i) the lymph from the foot and ankle drains into lymphatics which run with the deep veins to the popliteal node;(ii) the superficial lymphatics of the medial skin from mid-calf to the groin enter the inguinal node while those of the lateral skin drain into the popliteal node;(iii) the lymph draining the muscles collects in vessels which do not enter the popliteal node but join the femoral lymphatic post-nodally.2. The lymphatic system of the hind limb is regionalized so that lymph from a specific area enters the popliteal node in one specific lobe and no other.3. By cannulating the femoral lymphatic and ligating the post-nodal lymph vessel close to the point at which it leaves the node it was possible to collect pure muscle lymph.4. The mean muscle lymph flow was 21 mul./100 g.min whilst the skin lymph flow was 240 mul./100 g.min. The mean protein concentration of muscle lymph was usually somewhat higher than that of skin lymph.5. After nerve stimulation there was an increase in muscle lymph flow but no increase in protein concentration.6. After a mild thermal injury there was no change in muscle lymph flow or its protein concentration, but there was an enormous increase in the leakage of lactic dehydrogenase indicating considerable cellular injury. On the other hand a significant increase in both protein concentration and flow of skin lymph occurred after thermal injury.
Topics: Animals; Electric Stimulation; Hindlimb; Hot Temperature; Lymph; Lymph Nodes; Lymphatic System; Muscles; Proteins; Rabbits; Sciatic Nerve; Skin; Skin Physiological Phenomena
PubMed: 4763999
DOI: 10.1113/jphysiol.1973.sp010398 -
Annals of the New York Academy of... Oct 2010This minireview summarizes an oral presentation given at the National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health workshop... (Review)
Review
This minireview summarizes an oral presentation given at the National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health workshop "Lymphatics in the Digestive System: Physiology, Health, and Disease" in Bethesda, Maryland on November 3-4, 2009. The concepts of extrinsic and intrinsic pumps, as well as intrinsic and extrinsic flows, are discussed in relation to the lymph transport in mesenteric lymphatic vessels. Age-related alterations in the structure and regulatory mechanisms of lymph flow in mesenteric lymphatic vessels may provide the basis for their diminished ability to work during the periods of increased functional loads in them. The recent development of modern experimental tools provides the opportunity to extend the knowledge on lymph transport function of lymphatic vessels that is absolutely necessary to maintain fluid and macromolecular homeostasis and to provide a transportation route for lipids adsorbed in gut and to immune cells.
Topics: Aging; Animals; Humans; Lymph; Mesentery
PubMed: 20961301
DOI: 10.1111/j.1749-6632.2010.05710.x -
Microvascular Research Nov 2014Fluid homeostasis in vertebrates critically relies on the lymphatic system forming a hierarchical network of lymphatic capillaries and collecting lymphatics, for the... (Review)
Review
Fluid homeostasis in vertebrates critically relies on the lymphatic system forming a hierarchical network of lymphatic capillaries and collecting lymphatics, for the efficient drainage and transport of extravasated fluid back to the cardiovascular system. Blind-ended lymphatic capillaries employ specialized junctions and anchoring filaments to encourage a unidirectional flow of the interstitial fluid into the initial lymphatic vessels, whereas collecting lymphatics are responsible for the active propulsion of the lymph to the venous circulation via the combined action of lymphatic muscle cells and intraluminal valves. Here we describe recent findings on molecular and physical factors regulating the development and maturation of these two types of valves and examine their role in tissue-fluid homeostasis.
Topics: Animals; Biological Transport; Biomechanical Phenomena; Endothelial Cells; Extracellular Fluid; Homeostasis; Humans; Lymph; Lymphatic System; Lymphatic Vessels; Models, Animal; Models, Biological; Signal Transduction
PubMed: 25086182
DOI: 10.1016/j.mvr.2014.07.008 -
European Journal of Biochemistry Sep 19791. Human mesenteric lymph chylomicrons were isolated from chylous ascites fluid by ultra-centrifugation and agarose/gel chromatography and their apoprotein composition...
1. Human mesenteric lymph chylomicrons were isolated from chylous ascites fluid by ultra-centrifugation and agarose/gel chromatography and their apoprotein composition was analysed by dodecylsulfate/polyacrylamide gel electrophoresis, analytical isoelectric focusing and immuno-chemically. Major components of mesenteric lymph chylomicrons were apoprotein A-I, proteins of Mr less than 15 000 including the C-group apoproteins and a protein of Mr 46 000. Minor components were apoprotein E and a protein of Mr approximately equal to 200 000 (B-like protein). This apoprotein composition was qualitatively identical with that of chylomicrons from intestinal lymph of the rat, but was distinctly different from plasma chylomicrons of humans with fasting chylomicronaemia. 2. The protein of Mr approximately equal to 46 000 has been isolated by preparative dodecylsulfate/polyacrylamide gel electrophoresis from human and rat lymph chylomicrons and was compared to a protein of identical Mr present in rat high-density lipoproteins (apoplipoprotein A-IV) and in the rho less than 1.006 g/ml serum lipoprotein fraction of individual humans with alimentary hypertriglyceridaemia. In both species the 46 000-Mr proteins isolated from lymph and serum were identical according to amino acid composition and isoelectric point in 6 M urea. The human proteins from both sources were also immunologically identical. The similarities in the molecular properties of the human apolipoprotein and rat apolipoprotein A-IV indicate that these proteins are homologous. 3. Plasma levels of human apolipoprotein A-IV determined by electroimmunodiffusion were 14.15 +/- 3.66 mg/100 ml (n = 59), but greater than 90% of the protein was unassociated with the major lipoprotein fractions. It is concluded, that apolipoprotein A-IV is a main protein component of human lymph chylomicrons, that is removed from the particles in the plasma compartment.
Topics: Animals; Apolipoproteins; Apolipoproteins A; Centrifugation, Density Gradient; Chromatography, Gel; Chylomicrons; Electrophoresis, Polyacrylamide Gel; Humans; Immunodiffusion; Lymph; Mesentery; Rats
PubMed: 115688
DOI: 10.1111/j.1432-1033.1979.tb13261.x -
Journal of the Royal Society, Interface Apr 2012The lymphatic system is a vital part of the circulatory and immune systems, and plays an important role in homeostasis by controlling extracellular fluid volume and in... (Review)
Review
The lymphatic system is a vital part of the circulatory and immune systems, and plays an important role in homeostasis by controlling extracellular fluid volume and in combating infection. Nevertheless, there is a notable disparity in terms of research effort expended in relation to the treatment of lymphatic diseases in contrast to the cardiovascular system. While similarities to the cardiovascular system exist, there are considerable differences in their anatomy and physiology. This review outlines some of the challenges and opportunities for those engaged in modelling biological systems. The study of the lymphatic system is still in its infancy, the vast majority of the models presented in the literature to date having been developed since 2003. The number of distinct models and their variants are few in number, and only one effort has been made thus far to study the entire lymphatic network; elements of the lymphatic system such as the nodes, which act as pumps and reservoirs, have not been addressed by mathematical models. Clearly, more work will be necessary in combination with experimental verification in order to progress and update the knowledge on the function of the lymphatic system. As our knowledge and understanding of its function increase, new and more effective treatments of lymphatic diseases are bound to emerge.
Topics: Animals; Biomechanical Phenomena; Humans; Hydrodynamics; Lymph; Lymphatic System; Mathematical Concepts; Models, Biological; Systems Biology
PubMed: 22237677
DOI: 10.1098/rsif.2011.0751