Endothelial Glycocalyx and the Peritoneal Barrier

2008 ◽  
Vol 28 (1) ◽  
pp. 6-12 ◽  
Author(s):  
Michael F. Flessner

Recent advances in the study of the microcirculation have demonstrated the critical role of the endothelial glycocalyx in transcapillary transport from the plasma to the tissue interstitium. Since the capillary wall represents the initial resistance to solute transfer from the plasma through the tissue to the dialysate, the glycocalyx is potentially of major importance to peritoneal dialysis. Inadvertently removed in early histological studies, this thin, delicate layer of glycosaminoglycans and proteoglycans is now recognized as a primary barrier in transendothelial solute and water transport. Subperitoneal endothelia are exposed to inflammation, angiogenesis, and hyperglycemia, which have been shown to affect the layer by increasing permeability. This entity permits new hypotheses concerning the factors that influence the transport characteristics of peritoneal dialysis patients and provides new avenues of basic research into the fundamental mechanisms of alteration of the peritoneal barrier.

2018 ◽  
Vol 315 (6) ◽  
pp. F1732-F1746 ◽  
Author(s):  
Daiki Iguchi ◽  
Masashi Mizuno ◽  
Yasuhiro Suzuki ◽  
Fumiko Sakata ◽  
Shoichi Maruyama ◽  
...  

In a previous study of fungal peritoneal injury in peritoneal dialysis patients, complement (C)-dependent pathological changes were developed in zymosan (Zy)-induced peritonitis by peritoneal scraping. However, the injuries were limited to the parietal peritoneum and did not show any fibrous encapsulation of the visceral peritoneum, which differs from human encapsular peritoneal sclerosis (EPS). We investigated peritoneal injury in a rat model of Zy-induced peritonitis pretreated with methylglyoxal (MGO) instead of scraping (Zy/MGO peritonitis) to clarify the role of C in the process of fibrous encapsulation of the visceral peritoneum. Therapeutic effects of an anti-C5a complementary peptide, AcPepA, on peritonitis were also studied. In Zy/MGO peritonitis, peritoneal thickness, fibrin exudation, accumulation of inflammatory cells, and deposition of C3b and C5b-9 with loss of membrane C regulators were increased along the peritoneum until day 5. On day 14, fibrous encapsulation of the visceral peritoneum was observed, resembling human EPS. Peritoneal injuries and fibrous changes were significantly improved with AcPepA treatment, even when AcPepA was administered following injection of Zy in Zy/MGO peritonitis. The data show that C5a might play a role in the development of encapsulation-like changes in the visceral peritoneum in Zy/MGO peritonitis. AcPepA might have therapeutic effects in fungal infection-induced peritoneal injury by preventing subsequent development of peritoneal encapsulation.


2018 ◽  
Vol 38 (5) ◽  
pp. 381-384 ◽  
Author(s):  
Ali M. Shendi ◽  
Nathan Davies ◽  
Andrew Davenport

Previous reports linked systemic endotoxemia in dialysis patients to increased markers of inflammation, cardiovascular disease, and mortality. Many peritoneal dialysis (PD) patients use acidic, hypertonic dialysates, which could potentially increase gut permeability, resulting in systemic endotoxemia. However, the results from studies measuring endotoxin in PD patients are discordant. We therefore measured systemic endotoxin in 55 PD outpatients attending for routine assessment of peritoneal membrane function; mean age 58.7 ± 16.4 years, 32 (58.2%) male, 21 (38.2%) diabetic, median duration of PD treatment 19.5 (13 – 31) months, 32 (58.2%) using 22.7 g/L dextrose dialysates, and 47 (85.5%) icodextrin. The median systemic endotoxin concentration was 0.0485 (0.0043 – 0.103) Eu/mL. We found no association between endotoxin levels and patient demographics, markers of inflammation, serum albumin, N-terminal pro-brain natriuretic peptide, extracellular volume measured by bioimpedance, blood pressure, PD prescriptions or peritoneal membrane transporter status, or medications. The measurement of endotoxin can be lowered by failure to effectively release protein-bound endotoxin prior to analysis and increased by contamination when taking blood samples and processing and storing the samples. Additionally, contamination with β–glucan from fungal cell walls and the use of different assays to analyze endotoxin can also give differing results. These factors may help to explain the disparate results reported in different studies. Our study would suggest that exposure to standard peritoneal dialysates does not substantially increase systemic endotoxin. However, until endotoxin assays can measure free and bound endotoxin separately, the role of endotoxin causing inflammation in PD patients remains to be determined.


1996 ◽  
Vol 271 (6) ◽  
pp. H2254-H2262 ◽  
Author(s):  
O. Carlsson ◽  
S. Nielsen ◽  
el-R. Zakaria ◽  
B. Rippe

During peritoneal dialysis (PD), a major portion of the osmotically induced water transport to the peritoneum can be predicted to occur through endothelial water-selective channels. Aquaporin-1 (AQP-1) has recently been recognized as the molecular correlate to such channels. Aquaporins can be inhibited by mercurials. In the present study, HgCl2 was applied locally to the peritoneal cavity in rats after short-term tissue fixation, used to protect the tissues from HgCl2 damage. Dianeal (3.86%) was employed as dialysis fluid, 125I-albumin as an intraperitoneal volume marker, and 51Cr-EDTA (constantly infused intravenously) to assess peritoneal small-solute permeability characteristics. Immunocytochemistry and immunoelectron microscopy revealed abundant AQP-1 labeling in capillary endothelium in peritoneal tissues, representing sites for HgCl2 inhibition of water transport. HgCl2 treatment reduced water flow and inhibited the sieving of Na+ without causing any untoward changes in microvascular permeability, compared with that of fixed control rats, in which the peritoneal cavity was exposed to tissue fixation alone. In fixed control rats, the mean intraperitoneal volume (IPV) increased from 20.5 +/- 0.15 to 25.0 +/- 0.52 ml in 60 min, whereas in the HgCl2-treated rats, the increment was only from 20.7 +/- 0.23 to 23.5 +/- 0.4 ml. In fixed control rats, the dialysate Na+ fell from 135.3 +/- 0.97 to 131.3 +/- 1.72 mM, whereas in the HgCl2-treated rats the dialysate Na+ concentration remained unchanged between 0 and 40 min, further supporting that water channels had been blocked. Computer simulations of peritoneal transport were compatible with a 66% inhibition of water flow through aquaporins. The observed HgCl2 inhibition of transcellular water channels strongly indicates a critical role of aquaporins in PD and provides evidence that water channels are crucial in transendothelial water transport when driven by crystalloid osmosis.


Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2711
Author(s):  
Maria Mancini ◽  
Silvia Bassani ◽  
Maria Passafaro

During brain development, neurons need to form the correct connections with one another in order to give rise to a functional neuronal circuitry. Mistakes during this process, leading to the formation of improper neuronal connectivity, can result in a number of brain abnormalities and impairments collectively referred to as neurodevelopmental disorders. Cell adhesion molecules (CAMs), present on the cell surface, take part in the neurodevelopmental process regulating migration and recognition of specific cells to form functional neuronal assemblies. Among CAMs, the members of the protocadherin (PCDH) group stand out because they are involved in cell adhesion, neurite initiation and outgrowth, axon pathfinding and fasciculation, and synapse formation and stabilization. Given the critical role of these macromolecules in the major neurodevelopmental processes, it is not surprising that clinical and basic research in the past two decades has identified several PCDH genes as responsible for a large fraction of neurodevelopmental disorders. In the present article, we review these findings with a focus on the non-clustered PCDH sub-group, discussing the proteins implicated in the main neurodevelopmental disorders.


2002 ◽  
Vol 4 (2) ◽  
pp. 90-94 ◽  
Author(s):  
Kai-Ming CHOW ◽  
Wai-Shan WONG ◽  
Viola Chi-Ying CHOW ◽  
Teresa Yuk-Hwa WONG ◽  
Natalie Pui-Ha CHAN ◽  
...  

2003 ◽  
Vol 64 ◽  
pp. S84-S93 ◽  
Author(s):  
Ruth Mackenzie ◽  
Clifford J. Holmes ◽  
Suzanne Jones ◽  
John D. Williams ◽  
Nicholas Topley

2021 ◽  
Vol 12 ◽  
Author(s):  
Weina Wang ◽  
Liyan Shui ◽  
Yanning Liu ◽  
Min Zheng

Previous studies have reported an important role of c-kit in embryogenesis and adulthood. Activation of the SCF/KIT signal transduction pathway is customarily linked to cell proliferation, migration and survival thus influence hematopoiesis, pigmentation, and spermatogenesis. The role of c-kit in the liver is controversial, it is however argued that it is a double-edged sword in liver regeneration and diseases. First, liver c-kit+ cells, including oval cells, bile epithelial cells, and part of hepatocytes, participate in liver tissue repair by regenerating target cells according to the type of liver injury. At the same time, c-kit+ mast cells, act as immature progenitors in circulation, playing a critical role in liver fibrosis. Furthermore, c-kit is also a proto-oncogene. Notably, c-kit overexpression regulates gastrointestinal stromal tumors. Various studies have explored on c-kit and hepatocellular carcinoma, nevertheless, the intricate roles of c-kit in the liver are largely understudied. Herein, we extensively summarize previous studies geared toward providing hints for future clinical and basic research.


2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii520-iii521
Author(s):  
Kultigin Turkmen ◽  
Levent Demirtas ◽  
Emin M Akbas ◽  
Mutlu Buyuklu ◽  
Eftal Bakirci ◽  
...  

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