scholarly journals Lymphatic Reconstruction in Kidney Allograft Aggravates Chronic Rejection by Promoting Alloantigen Presentation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinwen Lin ◽  
Ying Chen ◽  
Huijuan Zhu ◽  
Kai Cheng ◽  
Huiping Wang ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Chronic Rejection ◽  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Lymphatic Vessels ◽  
Transplantation Rejection ◽  
Lower Egfr ◽  
Chemokine Ligand ◽  
Antigen Presenting

Chronic rejection of the renal allograft remains a major cause of graft loss. Here, we demonstrated that the remodeling of lymphatic vessels (LVs) after their broken during transplantation contributes to the antigen presenting and lymph nodes activating. Our studies observed a rebuilt of interrupted lymph draining one week after mouse kidney transplantation, involving preexisting lymphatic endothelial cells (LECs) from both the donor and recipient. These expanding LVs also release C-C chemokine ligand 21 (CCL21) and recruit CCR7+ cells, mainly dendritic cells (DCs), toward lymph nodes and spleen, evoking the adaptive response. This rejection could be relieved by LYVE-1 specific LVs knockout or CCR7 migration inhibition in mouse model. Moreover, in retrospective analysis, posttransplant patients exhibiting higher area density of LVs presented with lower eGFR, severe serum creatinine and proteinuria, and greater interstitial fibrosis. These results reveal a rebuilt pathway for alloantigen trafficking and lymphocytes activation, providing strategies to alleviate chronic transplantation rejection.

scholarly journals Clinical and Pathological Analyses of Borderline Changes Cases after Kidney Transplantation

Nephron ◽  
2020 ◽  
pp. 1-6
Author(s):  
Tomokazu Shimizu
Keyword(s):  
Renal Allograft ◽  
Interstitial Fibrosis ◽  
Graft Loss ◽  
Graft Function ◽  
Renal Transplant Recipients ◽  
Tubular Atrophy ◽  
Renal Graft ◽  
Interstitial Inflammation ◽  
Biopsy Specimens ◽  
Allograft Biopsy

<b><i>Aim:</i></b> We aimed to perform a clinicopathological analysis of cases presenting with borderline changes (BC) after renal transplantation and discuss whether BC might be clinically or pathologically important. <b><i>Materials and Methods:</i></b> BC was diagnosed in 22 renal allograft biopsy specimens obtained from 20 renal transplant recipients between April 2010 and March 2019 after follow-up at the Department of Transplant Surgery, Kidney Center, Toda Chuo General Hospital. <b><i>Results:</i></b> BC was diagnosed at a median of 500 days following transplantation. Among the 22 renal allograft biopsy specimens showing evidence of BC, tubulitis was observed in all specimens. Interstitial inflammation was present in 18 specimens (82%), peritubular capillaritis in 14 (64%), interstitial fibrosis (ci) and tubular atrophy (ct) in 4 (18%), and C4d deposition in the peritubular capillary was present in 6 specimens (27%). Glomerulitis and intimal arteritis were not observed. There was no renal graft loss during the observation period, but deterioration of renal allograft function after biopsy occurred in 9 patients (45%). <b><i>Conclusions:</i></b> In BC, tubulitis and interstitial inflammation were the main constituents. Because glomerulitis was not observed in our study, we suspect that BC contributes to acute T-cell-mediated rejection. Although BC did not lead to renal graft loss, renal graft function deterioration was seen in nearly half of the patients after the renal graft biopsy. We conclude that BC is important clinically and pathologically and needs to be monitored and treated appropriately.

scholarly journals Glucocorticoids stimulate the contractile activity of lymphatic vessels and lymph nodes

2017 ◽  
Vol 16 (4) ◽  
pp. 73-79
Author(s):  
G. I. Lobov ◽  
D. V. Unt
Keyword(s):  
Smooth Muscle ◽  
Lymph Nodes ◽  
Smooth Muscle Cells ◽  
Contractile Function ◽  
Contractile Activity ◽  
Lymphatic Vessels ◽  
Muscle Cells ◽  
Mechanisms Of Action ◽  
Genomic Effects ◽  
Antigen Presenting

Objective. The lymphatic network participates in the launch and development of an immune response. From an immunological point of view, the lymph flow, provided by active contractions of the lymphatic vessels, is the process of delivering antigens and antigen-presenting cells to the lymph nodes. The purpose of this study is to study the non-genomic effects and mechanisms of action of glucocorticoids, which are natural immunomodulators, on the transport function of lymphatic vessels and lymph nodes. Materials and methods. Bovine mesenteric afferent lymphatic vessels 1.2-1.5 mm in diameter and lymph nodes were used for the study. The contractile activity of isolated lymphatic vessels and capsules of lymph nodes under the action of glucocorticoids in vitro were studied. Agonists and antagonists of signaling pathways were used to determine the mechanisms of action of glucocorticoids on smooth muscle cells. Results and their discussion. Glucocorticoids in therapeutic concentrations increase the tone of lymphatic vessels and lymph nodes, increase in frequency and a decrease the amplitude of phase contractions. It is shown that glucocorticoids stimulate α-adrenoreceptors of smooth muscle cells due to the increase in their affinity. Glucocorticoids activate in the smooth muscle cells the RhoA / ROCK signaling pathway and inhibit the synthesis of endothelial vasodilators - NO and prostacyclin. The revealed changes in the contractile function of lymphatic vessels and lymph nodes under the action of glucocorticoids underlie the modulation of glucocorticoid transport of lymph and the speed of delivery to the lymph nodes of antigens and antigen-presenting cells, i.e. regulation of immune responses. Conclusions. Non-genomic effects and mechanisms of action of glucocorticoids on the contractile function of lymphatic vessels and nodes have been studied. Glucocorticoids activate smooth muscle cells of lymphatic vessels and nodes by stimulating α-adrenoreceptors, and also inhibit the production of NO and prostacyclin.

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.

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.

Neural glymphatic system: Clinical implications and potential importance of melatonin

2021 ◽  
Vol 4 (4) ◽  
pp. 551-565
Author(s):  
Ryan D Bitar ◽  
Jorge L Torres-Garza ◽  
Russel J Reiter ◽  
William T Phillips
Keyword(s):  
Lymph Nodes ◽  
Subarachnoid Space ◽  
Slow Wave Sleep ◽  
Lymphatic Vessels ◽  
Amyloid Β ◽  
Secretory Product ◽  
Cervical Lymph Nodes ◽  
Waste Products ◽  
Glymphatic System ◽  
The Brain

The central nervous system was thought to lack a lymphatic drainage until the recent discovery of the neural glymphatic system.  This highly specialized waste disposal network includes classical lymphatic vessels in the dura that absorb fluid and metabolic by-products and debris from the underlying cerebrospinal fluid (CSF) in the subarachnoid space. The subarachnoid space is continuous with the Virchow-Robin peri-arterial and peri-vascular spaces which surround the arteries and veins that penetrate into the neural tissue, respectively.  The dural lymphatic vessels exit the cranial vault via an anterior and a posterior route and eventually drain into the deep cervical lymph nodes. Aided by the presence of aquaporin 4 on the perivascular endfeet of astrocytes, nutrients and other molecules enter the brain from peri-arterial spaces and form interstitial fluid (ISF) that baths neurons and glia before being released into peri-venous spaces.  Melatonin, a pineal-derived secretory product which is in much higher concentration in the CSF than in the blood, is believed to follow this route and to clear waste products such as amyloid-β from the interstitial space. The clearance of amyloid-β reportedly occurs especially during slow wave sleep which happens concurrently with highest CSF levels of melatonin.  Experimentally, exogenously-administered melatonin defers amyloid-β buildup in the brain of animals and causes its accumulation in the cervical lymph nodes. Clinically, with increased age CSF melatonin levels decrease markedly, co-incident with neurodegeneration and dementia.  Collectively, these findings suggest a potential association between the loss of melatonin, decreased glymphatic drainage and neurocognitive decline in the elderly.

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