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American Journal of Physiology. Heart... Dec 2002The size of hyaluronan was compared between tissue and lymph using a combination of agarose gel electrophoresis and radiometric assay. Prenodal lymph was collected from...
The size of hyaluronan was compared between tissue and lymph using a combination of agarose gel electrophoresis and radiometric assay. Prenodal lymph was collected from heel skin and the gastrocnemius muscle in anesthetized rabbits. The major fraction of hyaluronan in both tissues had a molecular weight >4 million. Lymph contained primarily low-molecular-weight hyaluronan (<0.79 x 10(6)), which was absent from tissue. Volume loading produced a preferential increase in the flux of low-molecular-weight hyaluronan, indicating that tissue contains a small quantity of mobile, low-molecular-weight hyaluronan. The maximum daily removal of hyaluronan by lymph was <1% of the tissue content. The amount of lysosomal hyaluronidase activity in tissue was more than enough to account for a rapid turnover of hyaluronan. The data support the conclusion that lymph drainage is not significant in the normal catabolism of hyaluronan and may represent a small amount that becomes detached from the pericellular and extracellular matrixes.
Topics: Animals; Biological Transport; Female; Hindlimb; Hyaluronic Acid; Hyaluronoglucosaminidase; Liver; Lymph; Male; Muscle, Skeletal; Organ Size; Rabbits; Skin
PubMed: 12388305
DOI: 10.1152/ajpheart.00385.2002 -
Proceedings of the National Academy of... Jun 2012Skeletal muscle is widely perceived as nearly incompressible despite the fact that blood and lymphatic vessels within the endomysial and perimysial spaces undergo...
Skeletal muscle is widely perceived as nearly incompressible despite the fact that blood and lymphatic vessels within the endomysial and perimysial spaces undergo significant changes in diameter and length during stretch and contraction. These fluid shifts between fascicle and interstitial compartments have proved extremely difficult to measure. In this paper, we propose a theoretical framework based on a space-filling hexagonal fascicle array to provide predictions of the displacement of blood and lymph into and out of the muscle's endomysium and perimysium during stretch and contraction. We also use this model to quantify the distribution of blood and initial lymphatic (IL) vessels within a fascicle and its perimysial space using data for the rat spinotrapezius muscle. On average, there are 11 muscle fibers, 0.4 arteriole/venule pairs, and 0.2 IL vessels per fascicle. The model predicts that the blood volume in the endomysial space increases 24% and decreases 22% for a 20% contraction and stretch, respectively. However, these significant changes in blood volume in the endomysium produce a change of only ∼2% in fascicle cross-sectional area. In contrast, the entire muscle deviates from isovolumetry by 7% and 6% for a 20% contraction and stretch, respectively, largely attributable to the significantly larger blood volume changes that occur in the perimysial space. This suggests that arcade blood vessels in the perimysial space provide the primary pumping action required for the filling and emptying of ILs during muscular contraction and stretch.
Topics: Animals; Biomechanical Phenomena; Lymph; Models, Biological; Muscle Contraction; Muscle Tonus; Muscle, Skeletal; Rats; Regional Blood Flow
PubMed: 22615376
DOI: 10.1073/pnas.1206398109 -
Scientific Reports Jun 2019Secondary upper limb lymphoedema is usually caused by lymphatic system dysfunction. Diagnosis is primarily based on clinical features. However, there are no distinct...
Secondary upper limb lymphoedema is usually caused by lymphatic system dysfunction. Diagnosis is primarily based on clinical features. However, there are no distinct diagnostic criteria for lymphoedema. Although conventional lymphoscintigraphy is a useful technique to diagnose the severity of lymphoedema, the resultant data are two-dimensional. In this study, we examined the pathology of lymphoedema using single photon emission computed tomography-computed tomography lymphoscintigraphy (SPECT-CT LSG), a new technique that provides 3-dimensional information on lymph flow. We observed lymph flow pathways in the subcutaneous and muscle layers of the upper limbs. A significant positive correlation was found between the dermal back flow (DBF) type and the visualization of lymph nodes around the clavicle (p = 0.000266), the type of lymph flow pathways and the visualization of lymph nodes around the clavicle (p = 0.00963), and the DBF type and the lymph flow pathway (p = 0.00766). As the severity of lymphoedema increased, the DBF appeared more distally in the upper limb and the flow into the lymph nodes around the clavicle decreased, whereas the lymph flow pathways in the muscle layer became dominant. These findings demonstrate the features of lymphoedema pathology and the functional anatomy and physiology of the lymphatic system without the need for cadaver dissection.
Topics: Adult; Aged; Clavicle; Female; Humans; Lymph; Lymph Nodes; Lymphatic System; Lymphedema; Male; Middle Aged; Upper Extremity
PubMed: 31186436
DOI: 10.1038/s41598-019-44735-w -
Arteriosclerosis, Thrombosis, and... Apr 2020The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by...
OBJECTIVE
The lymphatic system is a circulatory system that unidirectionally drains the interstitial tissue fluid back to blood circulation. Although lymph is utilized by leukocytes for immune surveillance, it remains inaccessible to platelets and erythrocytes. Activated cells release submicron extracellular vesicles (EV) that transport molecules from the donor cell. In rheumatoid arthritis, EV accumulate in the joint where they can interact with numerous cellular lineages. However, whether EV can exit the inflamed tissue to recirculate is unknown. Here, we investigated whether vascular leakage that occurs during inflammation could favor EV access to the lymphatic system. Approach and Results: Using an in vivo model of autoimmune inflammatory arthritis, we show that there is an influx of platelet EV, but not EV from erythrocytes or leukocytes, in joint-draining lymph. In contrast to blood platelet EV, lymph platelet EV lacked mitochondrial organelles and failed to promote coagulation. Platelet EV influx in lymph was consistent with joint vascular leakage and implicated the fibrinogen receptor α2bβ and platelet-derived serotonin.
CONCLUSIONS
These findings show that platelets can disseminate their EV in fluid that is inaccessible to platelets and beyond the joint in this disease.
Topics: Animals; Arthritis, Rheumatoid; Blood Platelets; Capillary Permeability; Disease Models, Animal; Extracellular Vesicles; Lymph; Mice, Inbred C57BL; Serotonin
PubMed: 32102567
DOI: 10.1161/ATVBAHA.119.313698 -
American Journal of Physiology.... Nov 2008Mesenteric lymph contributes to normal homeostasis and has an emerging role in the pathogenesis of multiple organ dysfunction syndrome. The aim of this study was to...
Mesenteric lymph contributes to normal homeostasis and has an emerging role in the pathogenesis of multiple organ dysfunction syndrome. The aim of this study was to define the proteome of normal rodent mesenteric lymph in the fasted and fed states. Eight male Wistar rats fed a standard rodent diet were randomized to two groups. Group 1 (fasted, n = 4) were fasted for 24 h before anesthetized collection of mesenteric lymph. Group 2 (fed, n = 4) were allowed ad libitum access to food before lymph collection. Mesenteric lymph was subjected to proteomic analysis using iTRAQ and liquid chromatography-tandem mass spectrometry (LC-MS/MS). One hundred fifty proteins, including 26 hypothetical proteins, were identified in this study. All proteins were identified in lymph from both the fasted and fed states. The relative distribution profiles of protein functional classes in the mesenteric lymph differed significantly from that reported for plasma. The most abundant classes identified in lymph were protease inhibitors (16%) and proteins related to innate immunity (12%). In conclusion, this study provides the first detailed description of the normal mesenteric lymph proteome in the fed and fasted states using iTRAQ and LC-MS/MS.
Topics: Animals; Food Deprivation; Gene Expression Profiling; Gene Expression Regulation; Lymph; Male; Mesentery; Proteome; Rats; Rats, Wistar
PubMed: 18772360
DOI: 10.1152/ajpgi.90378.2008 -
The Journal of the American Osteopathic... Jul 2018By promoting the recirculation of tissue fluid, the lymphatic system preserves tissue health, aids in the absorption of gastrointestinal lipids, and supports immune...
CONTEXT
By promoting the recirculation of tissue fluid, the lymphatic system preserves tissue health, aids in the absorption of gastrointestinal lipids, and supports immune surveillance. Failure of the lymphatic system has been implicated in the pathogenesis of several infectious and inflammatory diseases. Thus, interventions that enhance lymphatic circulation, such as osteopathic lymphatic pump treatment (LPT), should aid in the management of these diseases.
OBJECTIVE
To determine whether thoracic duct lymph (TDL) mobilized during LPT would alter the function of macrophages in vitro.
METHODS
The thoracic ducts of 6 mongrel dogs were cannulated, and TDL samples were collected before (baseline), during, and 10 minutes after LPT. Thoracic duct lymph flow was measured, and TDL samples were analyzed for protein concentration. To measure the effect of TDL on macrophage activity, RAW 264.7 macrophages were cultured for 1 hour to acclimate. After 1 hour, cell-free TDL collected at baseline, during LPT, and after TDL was added at 5% total volume per well and co-cultured with or without 500 ng per well of lipopolysaccharide (LPS) for 24 hours. As a control for the addition of 5% TDL, macrophages were cultured with phosphate-buffered saline (PBS) at 5% total volume per well and co-cultured with or without 500 ng per well of LPS for 24 hours. After culture, cell-free supernatants were assayed for nitrite (NO2-), tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10). Macrophage viability was measured using flow cytometry.
RESULTS
Lymphatic pump treatment significantly increased TDL flow and the flux of protein in TDL (P<.001). After culture, macrophage viability was approximately 90%. During activation with LPS, baseline TDL, TDL during LPT, and TDL after LPT significantly decreased the production of NO2-, TNF-α, and IL-10 by macrophages (P<.05). However, no significant differences were found in viability or the production of NO2-, TNF-α, or IL-10 between macrophages cultured with LPS plus TDL taken before, during, and after LPT (P>.05).
CONCLUSION
The redistribution of protective lymph during LPT may provide scientific rationale for the clinical use of LPT to reduce inflammation and manage edema.
Topics: Animals; Cell Culture Techniques; Dogs; Lymph; Lymphatic System; Macrophages; Manipulation, Osteopathic; Thoracic Duct
PubMed: 29946663
DOI: 10.7556/jaoa.2018.099 -
Bio Systems Dec 2021By analogy with virions, the binding of biologically-inspired nanoparticles (NPs) with ligands to the cellular membrane containing receptors depends on the multivalent...
By analogy with virions, the binding of biologically-inspired nanoparticles (NPs) with ligands to the cellular membrane containing receptors depends on the multivalent ligand-receptor interaction, membrane bending, and cytoskeleton deformation. The interplay of these factors results in the existence of the potential minimum and activation barrier on the pathway towards full absorption of a NP. Herein, I hypothesize and show theoretically that the interaction of a NP, bound to one cell, with another cell can stabilize the potential minimum and increase the corresponding activation barrier, i.e., NPs can mediate the formation of long-living pairs of cells and aggregates containing a few cells inside blood and lymphatic vessels.
Topics: Animals; Blood Cells; Cell Aggregation; Humans; Lipid Bilayers; Lymph; Nanoparticles; Protein Multimerization
PubMed: 34597710
DOI: 10.1016/j.biosystems.2021.104551 -
Cellular & Molecular Immunology May 2021
Topics: Animals; CD8-Positive T-Lymphocytes; Immunologic Memory; Inflammation; Lymph; Lymph Nodes; Mice
PubMed: 32398805
DOI: 10.1038/s41423-020-0451-6 -
International Journal For Parasitology Sep 2014Infection of small ruminants with Teladorsagia circumcincta has, until now, been controlled using a combination of pasture management and frequent anthelmintic...
Infection of small ruminants with Teladorsagia circumcincta has, until now, been controlled using a combination of pasture management and frequent anthelmintic treatments. Resistance to the commonly used anthelmintics has driven research into the development of a subunit vaccine, encouraged by the demonstration of development of protective immunity in sheep following exposure to this parasite. Local immune effectors in the abomasum, in particular IgA, are thought to play important roles in naturally- and experimentally-acquired immunity. L3s represent the first contact of this pathogen with the host immune system and, herein, the presence of L3 antigen-specific IgA was demonstrated in abomasal mucus from immune sheep. This antibody source was used to immunoaffinity purify and identify IgA-reactive molecules present in L3s. We identified 155 different proteins in this way, including a number of activation-associated secretory proteins, venom allergen-like-type proteins, detoxifying enzymes, galectins and a suite of other potential vaccine candidate molecules. Levels of immunoaffinity-enriched L3 antigen-specific IgA in gastric lymph from previously-infected sheep were statistically significantly higher (P=0.004) than those measured in helminth-free sheep and a statistically significant negative correlation (P=0.005, rs=-0.565) was identified between immunoaffinity-enriched L3 antigen-specific IgA levels in efferent gastric lymph and total T. circumcincta burden measured at necropsy. In addition, a statistically significant positive correlation (P=0.007, rs=0.534) was measured between immunoaffinity-enriched L3 antigen-specific IgA levels in efferent gastric lymph and the percentage of inhibited L4s enumerated at necropsy. These results indicate that the purified antigens contain components that could be strongly considered as vaccine candidates.
Topics: Abomasum; Animals; Gastric Mucosa; Immunoglobulin A; Larva; Lymph; Mucus; Nematoda; Sheep; Transcriptome
PubMed: 25004076
DOI: 10.1016/j.ijpara.2014.05.007 -
Journal of Proteomics Jan 2013In this study a proteomic approach was used to define the protein content of matched samples of afferent prenodal lymph and plasma derived from healthy volunteers. The... (Clinical Trial)
Clinical Trial
In this study a proteomic approach was used to define the protein content of matched samples of afferent prenodal lymph and plasma derived from healthy volunteers. The analysis was performed using two analytical methodologies coupled with nanoliquid chromatography-tandem mass spectrometry: one-dimensional gel electrophoresis (1DEF nanoLC Orbitrap-ESI-MS/MS), and two-dimensional fluorescence difference-in-gel electrophoresis (2D-DIGE nanoLC-ESI-MS/MS). The 253 significantly identified proteins (p<0.05), obtained from the tandem mass spectrometry data, were further analyzed with pathway analysis (IPA) to define the functional signature of prenodal lymph and matched plasma. The 1DEF coupled with nanoLC-MS-MS revealed that the common proteome between the two biological fluids (144 out of 253 proteins) was dominated by complement activation and blood coagulation components, transporters and protease inhibitors. The enriched proteome of human lymph (72 proteins) consisted of products derived from the extracellular matrix, apoptosis and cellular catabolism. In contrast, the enriched proteome of human plasma (37 proteins) consisted of soluble molecules of the coagulation system and cell-cell signaling factors. The functional networks associated with both common and source-distinctive proteomes highlight the principal biological activity of these immunologically relevant body fluids.
Topics: Adult; Electrophoresis, Gel, Two-Dimensional; Electrophoresis, Polyacrylamide Gel; Gene Expression Profiling; Gene Expression Regulation; Humans; Lymph; Male; Mass Spectrometry; Plasma; Proteome; Proteomics
PubMed: 23202415
DOI: 10.1016/j.jprot.2012.11.013