scholarly journals In vivoquantification of lymph viscosity and pressure in lymphatic vessels and draining lymph nodes of arthritic joints in mice

2014 ◽  
Vol 592 (6) ◽  
pp. 1213-1223 ◽  
Author(s):  
Echoe M. Bouta ◽  
Ronald W. Wood ◽  
Edward B. Brown ◽  
Homaira Rahimi ◽  
Christopher T. Ritchlin ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Lymphatic Vessels ◽  
Arthritic Joints ◽  
Draining Lymph Nodes

scholarly journals Mast cell–derived particles deliver peripheral signals to remote lymph nodes

2009 ◽  
Vol 206 (11) ◽  
pp. 2455-2467 ◽  
Author(s):  
Christian A. Kunder ◽  
Ashley L. St. John ◽  
Guojie Li ◽  
Kam W. Leong ◽  
Brent Berwin ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mast Cell ◽  
Mast Cells ◽  
Tumor Necrosis Factor ◽  
Lymph Nodes ◽  
Tumor Necrosis ◽  
Lymphatic Vessels ◽  
Lymphoid Tissues ◽  
Draining Lymph Nodes ◽  
Necrosis Factor

During infection, signals from the periphery are known to reach draining lymph nodes (DLNs), but how these molecules, such as inflammatory cytokines, traverse the significant distances involved without dilution or degradation remains unclear. We show that peripheral mast cells, upon activation, release stable submicrometer heparin-based particles containing tumor necrosis factor and other proteins. These complexes enter lymphatic vessels and rapidly traffic to the DLNs. This physiological drug delivery system facilitates communication between peripheral sites of inflammation and remote secondary lymphoid tissues.

scholarly journals Infection-Induced Dermal Lymphatic Zippering Restricts Viral Dissemination from Skin and Promotes Anti-Viral CD8+ T Cell Expansion

2021 ◽  
Author(s):  
Madeline J. Churchill ◽  
Haley du Bois ◽  
Taylor A. Heim ◽  
Tenny Mudianto ◽  
Maria M. Steele ◽  
...  
Keyword(s):  
T Cell ◽  
Lymph Nodes ◽  
Vaccinia Virus ◽  
Host Defense ◽  
Lymphatic Vessels ◽  
T Cell Responses ◽  
Lymphatic Capillary ◽  
Viral Dissemination ◽  
Cell Responses ◽  
Draining Lymph Nodes

AbstractLymphatic vessels are often considered passive conduits that rapidly flush antigenic material, pathogens, and cells to draining lymph nodes. Recent evidence, however, suggests that lymphatic vessels actively regulate diverse processes from antigen transport to leukocyte trafficking and dietary lipid absorption. Here we tested the hypothesis that dermal lymphatic transport is dynamic and contributes to innate host defense during viral infection. We demonstrate that cutaneous vaccinia virus infection activates the tightening of lymphatic interendothelial junctions, termed zippering, in a VEGFA/VEGFR2-dependent manner. Both antibody-mediated blockade of VEGFA/VEGFR2 and lymphatic-specific deletion of Vegfr2 impaired lymphatic capillary zippering and increased fluid flux out of tissue. Strikingly, inhibition of lymphatic zippering allows viral dissemination to draining lymph nodes independent of dendritic cell migration and impairs CD8+ T cell priming. These data indicate that infection-induced dermal lymphatic capillary zippering is a context-dependent, active mechanism of innate host defense that limits interstitial fluid and virion flux and promotes protective, anti-viral CD8+ T cell responses.SummaryCutaneous infection with vaccinia virus induces VEGFR2-dependent dermal lymphatic capillary zippering. This tightening of lymphatic junctions exacerbates tissue edema, sequesters virus, and promotes anti-viral CD8+ T cell responses. Dermal lymphatic capillaries are therefore an active component of innate host defense.

scholarly journals Neutrophils rapidly migrate via lymphatics after Mycobacterium bovis BCG intradermal vaccination and shuttle live bacilli to the draining lymph nodes

Blood ◽  
2005 ◽  
Vol 106 (5) ◽  
pp. 1843-1850 ◽  
Author(s):  
Valérie Abadie ◽  
Edgar Badell ◽  
Patrice Douillard ◽  
Danielle Ensergueix ◽  
Pieter J. M. Leenen ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Mycobacterium Bovis ◽  
Lymphatic Vessels ◽  
Lymphoid Organ ◽  
Host Cells ◽  
Intradermal Vaccination ◽  
Bcg Vaccination ◽  
Inflammatory Monocytes ◽  
Draining Lymph Nodes

Abstract The early innate response after Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccination is poorly characterized but probably decisive for subsequent protective immunity against tuberculosis. Therefore, we vaccinated mice with fluorescent BCG strains in the ear dorsum, as a surrogate of intradermal vaccination in humans. During the first 3 days, we tracked BCG host cells migrating out of the dermis to the auricular draining lymph nodes (ADLNs). Resident skin dendritic cells (DCs) or macrophages did not play a predominant role in early BCG capture and transport to ADLNs. The main BCG host cells rapidly recruited both in the dermis and ADLNs were neutrophils. Fluorescent green or red BCG strains injected into nonoverlapping sites were essentially sheltered by distinct neutrophils in the ADLN capsule, indicating that neutrophils had captured bacilli in peripheral tissue and transported them to the lymphoid organ. Strikingly, we observed BCG-infected neutrophils in the lumen of lymphatic vessels by confocal microscopy on ear dermis. Fluorescence-labeled neutrophils injected into the ears accumulated exclusively into the ipsilateral ADLN capsule after BCG vaccination. Thus, we provide in vivo evidence that neutrophils, like DCs or inflammatory monocytes, migrate via afferent lymphatics to lymphoid tissue and can shuttle live microorganisms. (Blood. 2005;106: 1843-1850)

scholarly journals Ex vivo Demonstration of Functional Deficiencies in Popliteal Lymphatic Vessels from TNF-Tg Mice with Inflammatory Arthritis

2020 ◽  
Author(s):  
Joshua P. Scallan ◽  
Echoe M. Bouta ◽  
Homaira Rahimi ◽  
H. Mark Kenney ◽  
Christopher T. Ritchlin ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Repeated Measures ◽  
Inflammatory Arthritis ◽  
Ex Vivo ◽  
Lymphatic Vessels ◽  
Chronic Inflammatory Arthritis ◽  
Wide Range ◽  
Nos Inhibitors ◽  
Draining Lymph Nodes

AbstractBackgroundRheumatoid arthritis (RA) is a progressive immune-mediated inflammatory disease characterized by intermittent episodes of pain and inflammation in affected joints, or flares. Recent studies demonstrated lymphangiogenesis and expansion of draining lymph nodes during chronic inflammatory arthritis, and lymphatic dysfunction associated with collapse of draining lymph nodes in RA patients and TNF-transgenic (TNF-Tg) mice experiencing arthritic flare. As the intrinsic differences between lymphatic vessels afferent to healthy, expanding, and collapsed draining lymph nodes are unknown, we characterized the ex vivo behavior of popliteal lymphatic vessels (PLVs) from WT and TNF-Tg mice. We also interrogated the mechanisms of lymphatic dysfunction through inhibition of nitric oxide synthase (NOS).MethodsPopliteal lymph nodes (PLNs) in TNF-Tg mice were phenotyped as Expanding or Collapsed by in vivo ultrasound and age-matched to WT littermate controls. The PLVs were harvested and cannulated for ex vivo functional analysis over a relatively wide range of hydrostatic pressures (0.5 to 10 cmH2O) to quantify the end diastolic diameter (EDD), tone, amplitude (AMP), ejection fraction (EF), contraction frequency (FREQ) and fractional pump flow (FPF) with or without NOS inhibitors Data was analyzed using repeated measures two-way ANOVA with Bonferroni’s post hoc test.ResultsReal time videos of the cannulated PLVs demonstrated the predicted phenotypes of robust versus weak contractions of the WT versus TNF-Tg PLV, respectively. Quantitative analyses confirmed that TNF-Tg PLVs had significantly decreased AMP, EF and FPF versus WT (p<0.05). EF and FPF were recovered by NOS inhibition, while the reduction in AMP was NOS independent. No differences in EDD, tone, or FREQ were observed between WT and TNF-Tg PLVs, nor between Expanding versus Collapsed PLVs.ConclusionThese findings support the concept that chronic inflammatory arthritis leads to NOS dependent and independent draining lymphatic vessel dysfunction that exacerbates disease, and may trigger arthritic flare due to decreased egress of inflammatory cells and soluble factors from affected joints.

scholarly journals Progression of Metastasis through Lymphatic System

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 627
Author(s):  
Hengbo Zhou ◽  
Pin-ji Lei ◽  
Timothy P. Padera
Keyword(s):  
Lymph Node ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Lymphatic Vessels ◽  
Disease Status ◽  
Nodal Disease ◽  
Therapeutic Benefits ◽  
Node Metastases ◽  
Prognostic Power ◽  
Draining Lymph Nodes

Lymph nodes are the most common sites of metastasis in cancer patients. Nodal disease status provides great prognostic power, but how lymph node metastases should be treated is under debate. Thus, it is important to understand the mechanisms by which lymph node metastases progress and how they can be targeted to provide therapeutic benefits. In this review, we focus on delineating the process of cancer cell migration to and through lymphatic vessels, survival in draining lymph nodes and further spread to other distant organs. In addition, emerging molecular targets and potential strategies to inhibit lymph node metastasis are discussed.

scholarly journals Neutrophil Interactions with the Lymphatic System

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2106
Author(s):  
Arnolda Jakovija ◽  
Tatyana Chtanova
Keyword(s):  
Lymph Nodes ◽  
Lymphatic System ◽  
Neutrophil Migration ◽  
Lymphatic Vessels ◽  
High Endothelial Venules ◽  
Microbial Infections ◽  
Lymphatic Vasculature ◽  
Pathogen Control ◽  
Secondary Lymphoid Organs ◽  
Draining Lymph Nodes

The lymphatic system is a complex network of lymphatic vessels and lymph nodes designed to balance fluid homeostasis and facilitate host immune defence. Neutrophils are rapidly recruited to sites of inflammation to provide the first line of protection against microbial infections. The traditional view of neutrophils as short-lived cells, whose role is restricted to providing sterilizing immunity at sites of infection, is rapidly evolving to include additional functions at the interface between the innate and adaptive immune systems. Neutrophils travel via the lymphatics from the site of inflammation to transport antigens to lymph nodes. They can also enter lymph nodes from the blood by crossing high endothelial venules. Neutrophil functions in draining lymph nodes include pathogen control and modulation of adaptive immunity. Another facet of neutrophil interactions with the lymphatic system is their ability to promote lymphangiogenesis in draining lymph nodes and inflamed tissues. In this review, we discuss the significance of neutrophil migration to secondary lymphoid organs and within the lymphatic vasculature and highlight emerging evidence of the neutrophils’ role in lymphangiogenesis.

scholarly journals Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew K. Siggins ◽  
Nicola N. Lynskey ◽  
Lucy E. Lamb ◽  
Louise A. Johnson ◽  
Kristin K. Huse ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cancer Cells ◽  
Streptococcus Pyogenes ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Systemic Infection ◽  
Intracellular Pathogen ◽  
Infection Site ◽  
Local Infection ◽  
Draining Lymph Nodes

Abstract Unassisted metastasis through the lymphatic system is a mechanism of dissemination thus far ascribed only to cancer cells. Here, we report that Streptococcus pyogenes also hijack lymphatic vessels to escape a local infection site, transiting through sequential lymph nodes and efferent lymphatic vessels to enter the bloodstream. Contrasting with previously reported mechanisms of intracellular pathogen carriage by phagocytes, we show S. pyogenes remain extracellular during transit, first in afferent and then efferent lymphatics that carry the bacteria through successive draining lymph nodes. We identify streptococcal virulence mechanisms important for bacterial lymphatic dissemination and show that metastatic streptococci within infected lymph nodes resist and subvert clearance by phagocytes, enabling replication that can seed intense bloodstream infection. The findings establish the lymphatic system as both a survival niche and conduit to the bloodstream for S. pyogenes, explaining the phenomenon of occult bacteraemia. This work provides new perspectives in streptococcal pathogenesis with implications for immunity.

scholarly journals Ex vivo Demonstration of Functional Deficiencies in Popliteal Lymphatic Vessels From TNF-Transgenic Mice With Inflammatory Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Joshua P. Scallan ◽  
Echoe M. Bouta ◽  
Homaira Rahimi ◽  
H. Mark Kenney ◽  
Christopher T. Ritchlin ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Repeated Measures ◽  
Inflammatory Arthritis ◽  
Ex Vivo ◽  
Lymphatic Vessels ◽  
Chronic Inflammatory Arthritis ◽  
Wide Range ◽  
Nos Inhibitors ◽  
Draining Lymph Nodes

Background: Recent studies demonstrated lymphangiogenesis and expansion of draining lymph nodes during chronic inflammatory arthritis, and lymphatic dysfunction associated with collapse of draining lymph nodes in rheumatoid arthritis (RA) patients and TNF-transgenic (TNF-Tg) mice experiencing arthritic flare. As the intrinsic differences between lymphatic vessels afferent to healthy, expanding, and collapsed draining lymph nodes are unknown, we characterized the ex vivo behavior of popliteal lymphatic vessels (PLVs) from WT and TNF-Tg mice. We also interrogated the mechanisms of lymphatic dysfunction through inhibition of nitric oxide synthase (NOS).Methods: Popliteal lymph nodes (PLNs) in TNF-Tg mice were phenotyped as Expanding or Collapsed by in vivo ultrasound and age-matched to WT littermate controls. The PLVs were harvested and cannulated for ex vivo functional analysis over a relatively wide range of hydrostatic pressures (0.5–10 cmH2O) to quantify the end diastolic diameter (EDD), tone, amplitude (AMP), ejection fraction (EF), contraction frequency (FREQ), and fractional pump flow (FPF) with or without NOS inhibitors Data were analyzed using repeated measures two-way ANOVA with Bonferroni’s post hoc test.Results: Real time videos of the cannulated PLVs demonstrated the predicted phenotypes of robust vs. weak contractions of the WT vs. TNF-Tg PLV, respectively. Quantitative analyses confirmed that TNF-Tg PLVs had significantly decreased AMP, EF, and FPF vs. WT (p &lt; 0.05). EF and FPF were recovered by NOS inhibition, while the reduction in AMP was NOS independent. No differences in EDD, tone, or FREQ were observed between WT and TNF-Tg PLVs, nor between Expanding vs. Collapsed PLVs.Conclusion: These findings support the concept that chronic inflammatory arthritis leads to NOS dependent and independent draining lymphatic vessel dysfunction that exacerbates disease, and may trigger arthritic flare due to decreased egress of inflammatory cells and soluble factors from affected joints.

Infrared fluorescence lymphography in experimental and clinical practice

2018 ◽  
Vol 17 (2) ◽  
pp. 84-91 ◽  
Author(s):  
G. V. Papayan ◽  
A. L. Akopov ◽  
P. A. Antonyan ◽  
A. A. Ilin ◽  
N. N. Petrishchev
Keyword(s):  
Lymph Nodes ◽  
Near Infrared ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Diagnostic System ◽  
Biological Tissues ◽  
Peritumoral Injection ◽  
Intradermal Administration ◽  
Nir Fluorescence ◽  
Real Time Visualization

Introduction. Near infrared (NIR) fluorescent diagnostics is promising due to a deeper penetration into biological tissues. Material and methods. In experiments on rabbits and in clinical studies evaluation the lymphatic system with the use of the instrument complex FLUM-808 was analysed. Results. For visualization of the lymphatic vessels of the skin, the intradermal administration of ICG, dissolved in 20 % albumin in the order of 0.02 mg/ml, is optimal. Peritumoral injection of ICG allows visualizing sentinel lymph nodes in patients with lung cancer. Conclusions. The developed NIR fluorescence diagnostic system FLUM-808 allows to real time visualization of lymphatic vessels and lymph nodes.

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