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Review
. 2012:2012:484167.
doi: 10.1155/2012/484167. Epub 2012 Apr 10.

Pathophysiological changes to the peritoneal membrane during PD-related peritonitis: the role of mesothelial cells

Susan Yung  1 , Tak Mao Chan
Affiliations
Review

Pathophysiological changes to the peritoneal membrane during PD-related peritonitis: the role of mesothelial cells

Susan Yung et al. Mediators Inflamm. 2012.

Abstract

The success of peritoneal dialysis (PD) is dependent on the structural and functional integrity of the peritoneal membrane. The mesothelium lines the peritoneal membrane and is the first line of defense against chemical and/or bacterial insult. Peritonitis remains a major complication of PD and is a predominant cause of technique failure, morbidity and mortality amongst PD patients. With appropriate antibiotic treatment, peritonitis resolves without further complications, but in some PD patients excessive peritoneal inflammatory responses lead to mesothelial cell exfoliation and thickening of the submesothelium, resulting in peritoneal fibrosis and sclerosis. The detrimental changes in the peritoneal membrane structure and function correlate with the number and severity of peritonitis episodes and the need for catheter removal. There is evidence that despite clinical resolution of peritonitis, increased levels of inflammatory and fibrotic mediators may persist in the peritoneal cavity, signifying persistent injury to the mesothelial cells. This review will describe the structural and functional changes that occur in the peritoneal membrane during peritonitis and how mesothelial cells contribute to these changes and respond to infection. The latter part of the review discusses the potential of mesothelial cell transplantation and genetic manipulation in the preservation of the peritoneal membrane.

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Figures

Figure 1
Figure 1
Mesothelial cells line the peritoneal membrane and play a crucial role in peritoneal homeostasis. Their apical surface is endowed with a glycocalyx that provides a protective barrier against abrasion, and a slippery, nonadhesive surface for intracoelomic movement (1). Through their ability to synthesize various cytokines, growth factors, and matrix protein components, mesothelial cells actively participate in tissue repair and induction and resolution of peritoneal inflammation (2). Synthesis of matrix proteins by mesothelial cells may be incorporated into the underlying basement membrane on which mesothelial cells adhere to. Mesothelial cells facilitate in the transport of fluids and solutes across the peritoneal membrane (3), are the first line of defense against bacterial peritonitis (4), and can maintain a chemotactic gradient to assist in leukocyte infiltration (5) during peritoneal inflammation. The submesothelium contains sparse fibroblasts, collagen fibrils and capillaries. Changes to the structural integrity of the peritoneal membrane are invariably observed in PD patients. Constant exposure of the peritoneum to PD fluids, together with peritonitis, results in a reduction of the glycocalyx volume and a concomitant loss of anionic charge in the glycocalyx (6). Alterations in the anionic charge of the peritoneum can result in the reduction in the length and density of microvilli on the surface of mesothelial cells (7). Chronic exposure to PD fluid and peritonitis can induce detachment of mesothelial cells from their underlying basement membrane (8) resulting in partial (9) or complete denudation of the mesothelium. A loss of cell-cell interaction between mesothelial cells permits PD fluid to enter into the submesothelium (10). Increased synthesis of proinflammatory cytokines and matrix proteins is observed following the activation of infiltrating and resident peritoneal cells (11), leading to morphological changes such as reduplication of the basement membrane (12), induction of EMT in mesothelial cells, a breakdown of the basement membrane and their migration into the submesothelium (13). Transdifferentiated mesothelial cells have a greater fibrogenic potential and thus contribute to the deposition of matrix proteins and fibrin in the submesothelium (14), which if not controlled will lead to thickening of the submesothelium and ultimately peritoneal fibrosis and sclerosis. A loss of the protective mesothelium allows PD fluid and toxins released by bacteria to induce the activation of peritoneal fibroblasts (15), hyalinization of blood vessels, and vasculopathy (16). Such detrimental changes to the peritoneal membrane will significantly suppress the dialytic potential of the peritoneal membrane, which will invariably lead to the cessation of treatment.
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