Loss of Mesothelial Electronegative Fixed Charges during Murine Septic Peritonitis

Abstract

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.

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

“…Results are expressed as mean Ϯ SD of four separate experiments. within the mesothelium and the underlying basal lamina by chemical or bacterial injury has also been documented (7,8).…”

“…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.…”

Pathophysiological Changes to the Peritoneal Membrane during PD-Related Peritonitis: The Role of Mesothelial Cells

“…Accumulation of plasma proteins in the peritoneal cavity and their subsequent loss from the patient following the exchange of PD fluid is often observed during peritonitis [85, 117]. It can perhaps be likened to proteinuria whereby a loss of heparan sulfate proteoglycans, such as perlecan or agrin, in the glomerular basement membrane (GBM) results in the increased permeability of the GBM to anionic macromolecules such as albumin [118, 119].…”

“…In an experimental model of septic peritonitis whereby rats were administered live E. coli by intraperitoneal injection, a significant reduction in anionic sites at these locations was observed, which was accompanied by increased transperitoneal passage of proteins [85]. Although the nature of these anionic sites was not further investigated by these researchers, it is possible that perlecan may contribute at least in part to the anionic staining.…”

The Association Between Peritoneal Charge Barrier Dysfunction and Protein Lost During Continuous Ambulatory Peritoneal Dialysis

“…Thus, it is generally believed that disruption of the peritoneal barrier will cause negatively charged molecules (such as albumin) to pass through more readily, leading to significant protein loss [11], although there is some question about the relative importance of the peritoneum as a molecular barrier vs. a charge barrier [12]. However, the effect of disruption of the peritoneal charge barrier on protein loss in PD patients has not yet been established.…”