Electrolyte and Fluid Transport in Mesothelial Cells

Abstract

Mesothelial cells are specialized epithelial cells, which line the pleural, pericardial, and peritoneal cavities. Accumulating evidence suggests that the monolayer of mesothelial cells is permeable to electrolyte and fluid, and thereby govern both fluid secretion and re-absorption in the serosal cavities. Disorders in these salt and fluid transport systems may be fundamental in the pathogenesis of pleural effusion, pericardial effusion, and ascites. In this review, we discuss the location, physiological function, and regulation of active transport (Na + -K + -ATPase) systems, cation and anion channels (Na + , K + , Cl − , and Ca 2+ channels), antiport (exchangers) systems, and symport (co-transporters) systems, and water channels (aquaporins). These secretive and absorptive pathways across mesothelial monolayer cells for electrolytes and fluid may provide pivotal therapeutical targets for novel clinical intervention in edematous diseases of serous cavities. Keywords mesothelioma; ion channel; permeability; effusion; filtration; ENaC Mesothelial cells are specialized epithelial cells that line the serous cavities, including the pleural, pericardial, and peritoneal cavities in addition to internal organs [1]. While the mesothelium was first described more than a century ago, one of its critical essential functions, namely, its active roles in transerosal transport, in particular, cavity fluid secretion and reabsorption, was long overlooked. Only in last two decades compelling evidence accumulated that mesothelial cells actively transport electrolytes and fluid and, in turn, regulate liquid volume within the cavities. The mesothelium, on the basis of recent increasing experimental evidence, both in vitro and in vivo, is less permeable to electrolytes than was previously assumed, with ion permeability characteristics similar to those in epithelia [2,3]. Herein this article we will review the expression and biophysical features of salt and fluid transport systems, both active and passive, that have been identified in mesothelial cells (Fig. 1, Tables 1 and 2). I. ION CHANNELS AND ATPASE I-1. Amiloride-Inhibitable Cation ChannelsThe epithelial sodium channel (ENaC), as a major pathway which participates in sodium movement across the apical membrane of polarized epithelial cells, has been cloned and characterized [4][5][6] ENaC subunits have been cloned to date, namely α-, β-, γ-, δ-, and ε-ENaC [7]. The biophysical properties of various ENaC channels depend on their subunit compositions. When expressed in oocytes one of "conductive" subunits (α, δ, and ε-ENaC) can form a channel sharing identical biophysical properties to three-subunit channels composed of both a "conductive" subunit and two "non-conductive" subunits, namely, β-and γ-ENaCs. When α-, β-, and γ-ENaC subunits are assembled together, the result is a 4-to 6-pS channel that is highly selective for Na + over K + . In contrast, two-subunit α β-and α γ-ENaC channels display diverse amiloride sensitivity, conductance, and Na + permeability [8]. ENaC is...

Dexamethasone decreases the transmesothelial electrical resistance of the parietal and visceral pleura

“…The early proofs of the importance of mesothelial ionic transporters are derived from in vivo experiments in rabbits where inhibitors of these transporters reduced pleural fluid absorption rates [2]. Later in vitro studies using the same inhibitors had similar results as interpreted by the increase in the transmesothelial resistance that was observed [3,[12][13][14][15][16]. The above suggest that although the electrical resistance of the pleura is much lower than other epithelia, it is an important regulator of solute coupled liquid absorption, which is one of the main mechanisms of pleural fluid turnover.…”

“…In these cases, administration of corticosteroids results in acceleration of the effusion resolution through a mechanism that is generally attributed to the anti-inflammatotry effects of steroids [1]. In physiological conditions solute coupled liquid absorption through the mesothelium is the main pathway of pleural fluid absorption, while in pleural effusions lymphatic drainage is the main route of fluid absorption [2][3][4].…”

Effusion-Serum Chloride Gradient in Heart Failure-Associated Pleural Effusion ― Pathophysiologic Implications ―

“… 42 These mesothelial cells are recognized as active cells, involved in many structural and metabolic functions. 30 , 43 In addition to these mesothelial cell functions, 30 , 43 it is important to determine whether anionic Cl − truly and selectively penetrate the pleural-associated capillary endothelial glycocalyx layer, 44 diffuse into the pleural space, and hold pleural fluid as a result of their tonic effect under conditions of insufficient drainage via venous and/or lymphatic channels in association with the effects of HF status on the function of the endothelial glycocalyx layer. 45 , 46 Other related mechanisms of transcapillary exchange of solutes 47 , 48 in and around the pleural space should also be examined with regard to the formation of HF-related pleural effusion.…”

Use of Mesothelial Cells and Biological Matrices for Tissue Engineering of Simple Epithelium Surrogates

“…Biostructurally, the mesothelium represents a semi-permeable laminar interface that separate fluid-filled body cavities from blood vessels and lymphatics running within the underneath submesothelial connective tissue layers. Besides its property of physical barrier, the mesothelium acts also as bioactive interface regulating fluid flows interchanges across its surface to maintain an optimal osmolarity and ionic activity of body cavity fluids; these functions are mainly accomplished by transmembrane ion pumps (Na + /K + -ATPase) and water channels (aquaporins) (Witowski et al, 1997 ; Ji and Nie, 2008 ). Among other main functions, mesothelial cells also secrete lubricants that stay electrochemically entrapped between their numerous surface microvilli to create a lubricated thin film or glycocalyx allowing the free sliding of opposite parietal and visceral mesotheliums with minimal abrasion (Mutsaers, 2002 ).…”

“…The mesothelial glycocalyx is mainly composed by glycosaminoglycans, especially hyaluronan, a large anionic polymer of disaccharides with high hydrophilicity which forms a highly hydrated gel layer (Yung and Chan, 2007 ). Mesothelial cells also actively regulate celomic cavities homeostasis and inflammatory status via their secretion of numerous pro- and anti-inflammatory cytokines (Lanfrancone et al, 1992 ; Mutsaers and Wilkosz, 2007 ; Ji and Nie, 2008 ). It has also been evidenced that mesothelial cells are actively recruited during serosal regeneration, through processes of proliferation, migration or delamination, and secretion of a large variety of growth factors or cytokines (Foley-Comer et al, 2002 ; Mutsaers, 2002 ; Herrick and Mutsaers, 2004 ; Mutsaers, 2004 ; Mutsaers and Wilkosz, 2007 ; Carmona et al, 2011 ).…”