Ruthenium-Red-Stained Polyanionic Fixed Charges in Peritoneal Microvessels

Gotloib, Lázaro; Sella, P. Bar; Jaichenko, José; Shustack, Allan

doi:10.1159/000184451

Cited by 44 publications

(14 citation statements)

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“…Although their physiological significance is less clear, the working hypothesis is that they retard the passage of molecules of similar charge a n d /o r accelerate that of molecules with opposite polarity. This is certainly true of anionic charges on glomerular and intestinal capillaries [5][6][7], Previous studies in our laboratory showed the exis tence of anionic charges on the peritoneal basement membrane and capillaries subjacent to it [8,9]. Recently we demonstrated that these charges are greatly reduced under conditions of local or generalized inflammation (during peritonitis and sepsis), reverting to normal num bers within 14 days after the acute phase of the episode [10,11].…”

Section: Introductionmentioning

confidence: 81%

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Protamine Sulfate Induces Enhanced Peritoneal Permeability to Proteins

Galdi¹,

Shostak²,

Jaichenko³

et al. 1991

Nephron

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We present a direct link between the neutralization of anionic sites by intraperitoneal protamine and a rise in protein passage to the peritoneal cavity during isosmotic peritoneal dialysis in rabbits. Each experiment included two 1-hour exchanges. No drugs were added in the first exchange. In group A (control) there were no drugs in the second hour either. In group B, protamine (50 μg/ml) was added to the second exchange volume. In group C, protamine and heparin (50 U/ml) were added. In groups A and C, appearance curves of metabolites during the first (baseline) and the second (experimental) hours were not statistically different. In group B, differences for urea, glucose and uric acid were not significant, but they were highly so for protein (increase of 100%, p < 0.01). Transperitoneal passage of albumin is substantially enhanced by protamine. Neutralization of protamine with heparin prevents this, showing that availability of anionic sites is the crucial limiting factor. Protamine did not significantly affect the transfer of small neutral molecules.

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Section: Introductionmentioning

confidence: 81%

“…Anionic charges are present at the various levels of the peritoneal barrier: microvilli, basement membrane, ca pillaries [8,9], Inflammatory mediators like bradykinin and histamine have little effect on urea clearance across it [36] and the polycation polyethyleneimine increases only water transport [37].…”

Section: Discussionmentioning

confidence: 99%

Protamine Sulfate Induces Enhanced Peritoneal Permeability to Proteins

Galdi¹,

Shostak²,

Jaichenko³

et al. 1991

Nephron

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“…Previous studies have shown the existence of continu ous electronegative charges along the mesothelial cell glycocalyx as well as along the basement membrane of both peritoneal mésothélium [18][19][20] and that of submesothelial capillaries and postcapillary venules [18,21], as well as a substantial reduction of the AS density distribu tion in mesenteric and diaphragmatic microvessels as a consequence of murine experimental septic peritonitis [22]. Therefore, a substantial reduction of the electrone gative charge of the microvascular and mesothelial bar riers could be a rational pathophysiological explanation for the increased protein losses observed during peritoni tis.…”

Section: Introductionmentioning

confidence: 99%

Loss of Mesothelial Electronegative Fixed Charges during Murine Septic Peritonitis

Gotloib¹,

Shustak²,

Jaichenko³

1989

Nephron

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Previous studies showed that murine septic peritonitis induced a substantial reduction of the anionic site density distribution in mesenteric and diaphragmatic microvessels. The present study shows that acute experimental septic peritonitis induces a severe reduction of the anionic site density distribution along the submesothelial basement membrane. Five days after induction of peritonitis, there was a partial recovery of anionic sites which even at 13 days was not completed. This observation suggests that the increased protein losses observed during peritonitis are the consequence of increased microvascular and mesothelial permeability to anionic plasma proteins secondary to neutralization and/or disappearance of the anionic sites located in the microvascular wall and in the mesothelial layer.

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“…Injury to the mesothelium represents an important initiating step, leading to the progressive histologic changes of the peritoneum in peritoneal dialysis (PD). The abundant anionic sites normally present in the mesothelium and the underlying basement membrane prevent excessive albumin wastage (5)(6)(7)(8). Proteoglycans (PG), which are anionic macromolecules present ubiquitously on the cell surface and in basement membrane (9,10), are putatively major contributors to the anionic sites in the peritoneum.…”

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confidence: 99%

Reduction of Perlecan Synthesis and Induction of TGF-β1 in Human Peritoneal Mesothelial Cells Due to High Dialysate Glucose Concentration

Yung¹,

Chen²,

Tsang³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Prolonged exposure of the peritoneal mesothelium to high dialysate glucose concentrations reduces anionic sites that are critical to its selective permeability, thereby impairing the peritoneal transport properties in patients on long-term peritoneal dialysis (PD). Perlecan, an anionic heparan sulfate proteoglycan, is pivotal to the selective permeability of basement membranes, and high glucose concentrations modulate its synthesis in mesangial cells. The effect of glucose on perlecan expression in the peritoneal mesothelium has not been established. We investigated perlecan expression in peritoneal biopsies from patients on PD, and the effect of high glucose concentrations on perlecan synthesis in cultured human peritoneal mesothelial cells (HPMC). Peritoneal biopsies from PD patients showed reduced perlecan expression compared with controls. Exposure of HPMC to high glucose concentrations resulted in a dose-dependent reduction in the synthesis of perlecan polypeptide and its deposition into the extracellular matrix. These effects were mediated in part through the induction of TGF-␤1. Characterization studies showed that perlecan synthesized by HPMC contained solely heparan sulfate glycosaminoglycan (HS GAG) chains, and [35 S]-incorporation studies demonstrated progressive reduction of their de novo synthesis with increasing glucose concentrations (68142 Ϯ 3658, 48147 Ϯ 2517, 31468 Ϯ 5781, and 25575 Ϯ 3621 cpm/g cellular protein for 5 mM, 30 mM, 75 mM, and 120 mM D-glucose, respectively; P Ͻ 0.001 for 5 mM versus 30 mM D-glucose, and P Ͻ 0.0001 for 5 mM versus 75 mM or 120 mM D-glucose). Both the length and the charge density of the HS GAG chains remained unchanged. Reduction of peritoneal perlecan expression in long-term PD was attributed to high dialysate glucose concentrations, which induced TGF-␤1 and reduced perlecan synthesis in HPMC. Since perlecan can sequester growth factors, thereby modulating cell migration and differentiation perturbation of peritoneal perlecan expression contributes to the structural and functional changes of the peritoneum in long-term PD.

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Ruthenium-Red-Stained Polyanionic Fixed Charges in Peritoneal Microvessels

Cited by 44 publications

References 13 publications

Protamine Sulfate Induces Enhanced Peritoneal Permeability to Proteins

Protamine Sulfate Induces Enhanced Peritoneal Permeability to Proteins

Loss of Mesothelial Electronegative Fixed Charges during Murine Septic Peritonitis

Reduction of Perlecan Synthesis and Induction of TGF-β1 in Human Peritoneal Mesothelial Cells Due to High Dialysate Glucose Concentration

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