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Paracellular Pathway (paracellular + pathway)
Selected AbstractsEndothelial barriers: from hypothetical pores to membrane proteins*JOURNAL OF ANATOMY, Issue 6 2002J. A. Firth Abstract The anatomical counterpart of the physiologically defined small pore system of capillary endothelia has proved difficult to establish. In non-brain continuous capillaries, the contributions of caveolar and transmembrane pathways are likely to be small and paracellular clefts are probably the dominant routes. Analogy with epithelial paracellular pathways suggests that tight junctions may be the most restrictive elements. However, structural features of tight junction-based models are incompatible with physiological data; it is more likely that the tight junction acts as a shutter limiting the available cleft area. Proposed molecular sieves elsewhere in the paracellular pathway include the glycocalyx and the cadherin-based complexes of the adherens junctions. The molecular architecture of tight junctions and adherens junctions is moderately well defined in terms of molecular species, and there are differences at both sites between the endothelial and epithelial spectra of protein expression. However, definition of the size-restricting pore remains elusive and may require structural biology approaches to the spatial arrangements and interactions of the membrane molecular complexes surrounding the endothelial paracellular clefts. [source] Impairment of blood,cerebrospinal fluid barrier properties by retrovirus-activated T lymphocytes: reduction in cerebrospinal fluid-to-blood efflux of prostaglandin E2JOURNAL OF NEUROCHEMISTRY, Issue 6 2005Seng Thuon Khuth Abstract The choroid plexus epithelium forms the interface between the blood and the CSF. In conjunction with the tight junctions restricting the paracellular pathway, polarized specific transport systems in the choroidal epithelium allow a fine regulation of CSF-borne biologically active mediators. The highly vascularized stroma delimited by the choroidal epithelium can be a reservoir for retrovirus-infected or activated immune cells. In this work, new insight in the implication of the blood,CSF barrier in neuroinfectious and inflammatory diseases is provided by using a differentiated cellular model of the choroidal epithelium, exposed to infected T lymphocytes. We demonstrate that T cells activated by a retroviral infection, but not non-infected cells, reduce the transporter-mediated CSF-to-blood efflux of organic anions, in particular that of the potent pro-inflammatory prostaglandin PGE2, via the release of soluble factors. A moderate alteration of the paracellular permeability also occurs. We identified the viral protein Tax, oxygenated free radicals, matrix-metalloproteinases and pro-inflammatory cytokines as active molecules released during the exposure of the epithelium to infected T cells. Among them, tumour necrosis factor and interleukin 1 are directly involved in the mechanism underlying the decrease in some choroidal organic anion efflux. Given the strong involvement of CSF-borne PGE2 in sickness behaviour syndrome, these data suggest that the blood,CSF barrier plays an important role in the pathophysiology of neuroinflammation and neuroinfection, via changes in the transport processes controlling the CSF biodisposition of PGE2. [source] Ileal Uptake of Polyalkylcyanoacrylate Nanocapsules in the RatJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2000CHRISTIANE DAMGÉ The ileal uptake of polyalkylcyanoacrylate nanocapsules (less than 300 nm in diameter) has been investigated in the rat. Iodised oil (Lipiodol) was used as the tracer for X-ray microprobe analysis in scanning electron microscopy. Lipiodol nanocapsules, or an emulsion of Lipiodol, were administered in the lumen of an isolated ileal loop of rat. Lipiodol nanocapsules improved the absorption of the tracer as indicated by increased concentrations of iodine in the mesenteric blood (+27%, P < 0.01, compared with Lipiodol emulsion). Intestinal biopsies were taken at different time points and the samples underwent cryofixation and freeze-drying. The nanocapsules were characterized by their strong iodine emission, and electron microscopy of the biopsy samples revealed nanocapsules in the intraluminal mucus of the non-follicular epithelium, then in the intercellular spaces between enterocytes, and finally the nanocapsules were found within intravillus capillaries. However, nanocapsules were most abundant in the Peyer's patches, where the intestinal epithelium had been crossed by way of the specialized epithelial cells, designated membranous cells, or M cells, and their adjacent absorptive cells. These observations were confirmed quantitatively by measuring iodine concentrations in the various tissue compartments. Ten minutes after the intraluminal administration of Lipiodol nanocapsules, the emission of iodine peaked in the mucus (+77%, P < 0.01), in M cells (+366%, P < 0.001), in enterocytes adjacent to M cells (+70%, P < 0.05) and in lymph vessels (+59%, P < 0.05). Polyalkylcyanoacrylate nanocapsules were able to pass through the ileal mucosa of the rat via a paracellular pathway in the non-follicular epithelium, and most predominantly, via M cells and adjacent enterocytes in Peyer's patches. [source] Biliary inorganic phosphate as a tool for assessing cold preservation-reperfusion injury: A study in the isolated perfused rat liver modelLIVER TRANSPLANTATION, Issue 2 2003Luciana L. Almada Ischemia-reperfusion injury is a major cause of early graft dysfunction after liver transplantation. The bile flow has been suggested as an index of ischemic damage, and severely impaired bile flow seems to be predictive of poor survival in experimental studies. Looking for injury markers, biliary inorganic phosphate has the potential of being a useful endogenous marker of diminished hepatobiliary function because this anion is excreted in the bile by a paracellular pathway and it can detect changes in permeability. The goal of this study was to evaluate the effects of cold preservation-reperfusion of the liver on bile flow and bile inorganic phosphate and their relationship with storage-related graft failure. The isolated and perfused rat liver was used to evaluate the injury for ischemia-reperfusion. The intrahepatic resistance, lactate dehydrogenase release, and potassium and biliary inorganic phosphate concentration were used to estimate viability and function of freshly isolated or cold-preserved livers. The intrahepatic resistance and the bile flow were consistent and significantly decreased throughout the perfusion time in relation to the increment in storage. Inorganic phosphate is more concentrated in bile from preserved livers, showing an alteration in paracellular pathway, confirmed by the biliary excretion of horseradish peroxidase. After preservation, concentration and excretion of the paracellular marker were increased during the first peak. The second peak appears earlier in preserved livers (10 minutes) with a different shape but without changes in concentration. In conclusion, inorganic phosphate in bile shows changes in paracellular permeability as occurs in livers after 48 hours of cold preservation. [source] The intestinal barrier and its regulation by neuroimmune factorsNEUROGASTROENTEROLOGY & MOTILITY, Issue 7 2010å. v. Keita Abstract Background, The ability to control uptake across the mucosa and protect from damage of harmful substances from the lumen is defined as intestinal barrier function. A disturbed barrier dysfunction has been described in many human diseases and animal models, for example, inflammatory bowel disease, irritable bowel syndrome, and intestinal hypersensitivity. In most diseases and models, alterations are seen both of the paracellular pathway, via the tight junctions, and of the transcellular routes, via different types of endocytosis. Recent studies of pathogenic mechanisms have demonstrated the important role of neuroimmune interaction with the epithelial cells in the regulation of barrier function. Neural impulses from extrinsic vagal and/or sympathetic efferent fibers or intrinsic enteric nerves influence mucosal barrier function via direct effects on epithelial cells or via interaction with immune cells. For example, by nerve-mediated activation by corticotropin-releasing hormone or cholinergic pathways, mucosal mast cells release a range of mediators with effects on transcellular, and/or paracellular permeability (for example, tryptase, TNF-,, nerve growth factor, and interleukins). Purpose, In this review, we discuss current physiological and pathophysiological aspects of the intestinal barrier and, in particular, its regulation by neuroimmune factors. [source] Claudin-5 is Restricted to the Tight Junction Region of Uterine Epithelial Cells in the Uterus of Pregnant/Gravid Squamate ReptilesTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 5 2008Joanna M. Biazik Abstract Claudin-5, a tight junctional protein associated with ion and size selectivity, has been found in the uterus of skinks. This study has generated critical information about the molecular assembly of the tight junction at various stages of the reproductive cycle in the skink uterus. Recent studies looking at tight junctional proteins found occludin expression in the tight junction region of uterine epithelial cells in the skink uterus; however, occludin did not disclose any further information about the ions and size of ions permeating across the paracellular pathway. A ,22-kDa claudin-5 band was detected in the uterus of the skinks present in this study and immunohistochemistry revealed that claudin-5 redistributes to the tight junction region of the lateral plasma membrane of uterine epithelial cells in late stage pregnancy/gravidity. This finding indicates that the tight junction becomes more assembled to precisely regulate ion and solute permeation in late stage pregnancy/gravidity. Claudin-5 with its functional role as a molecular sieve due to the formation of ion and size selective pores suggests that permeation of ions smaller than 0.8 kDa are restricted when claudin-5 is redistributed to the tight junction region of the later plasma membrane. This report is the first description of the molecular mechanisms that may be involved in regulating nutrient provision in the reptilian uterus. Anat Rec, 291:547,556, 2008. © 2008 Wiley-Liss, Inc. [source] Effect of lectins on the transport of food ingredients in Caco-2 cell culturesBIOFACTORS, Issue 1-4 2004Y. Ohno Abstract We investigated the effect of several lectins, such as soy bean lectin (SBA), concanavalin A (Con A), and wheat germ agglutinin (WGA), on the transport of some food ingredients (isoflavones, quercetin glycosides, carnosine/anserine) across Caco-2 cell monolayers. After incubation of food ingredients (0.03,2 mmol/L) in the presence or absence of lectins (1,180 ,/ml) on the apical side, aliquots were taken from the apical and basolateral solution, and were subjected to HPLC analysis. We also examined the effect of lectins on the permeability of the tight junction by measuring the transepithelial electrical resistance (TER) value of the Caco-2 cell monolayer. Isoflavones, which was not transported to the basolateral solution without lectins, could be transported in the presence of lectins, whereas their aglycones were detected at the same levels with or without the lectin treatment. The transport of quercetin glycosides also increased in the presence of lectins, however, that of peptides was not affected by the lectins. Con A and WGA, but SBA, decreased the TER value, indicating that Con A and WGA increased the transport via paracellular pathway, whereas SBA did via a different pathway. [source] The integration of digestion and osmoregulation in the avian gutBIOLOGICAL REVIEWS, Issue 4 2009Todd J. McWhorter Abstract We review digestion and osmoregulation in the avian gut, with an emphasis on the ways these different functions might interact to support or constrain each other and the ways they support the functioning of the whole animal in its natural environment. Differences between birds and other vertebrates are highlighted because these differences may make birds excellent models for study and may suggest interesting directions for future research. At a given body size birds, compared with mammals, tend to eat more food but have less small intestine and retain food in their gastrointestinal tract (GIT) for shorter periods of time, despite generally higher mass-specific energy demands. On most foods, however, they are not less efficient at digestion, which begs the question how they compensate. Intestinal tissue-specific rates of enzymatic breakdown of substrates and rates of active transport do not appear higher in birds than in mammals, nor is there a demonstrated difference in the extent to which those rates can be modulated during acclimation to different feeding regimes (e.g. diet, relative intake level). One compensation appears to be more extensive reliance on passive nutrient absorption by the paracellular pathway, because the avian species studied so far exceed the mammalian species by a factor of at least two- to threefold in this regard. Undigested residues reach the hindgut, but there is little evidence that most wild birds recover microbial metabolites of nutritional significance (essential amino acids and vitamins) by re-ingestion of faeces, in contrast to many hindgut fermenting mammals and possibly poultry. In birds, there is some evidence for hindgut capacity to breakdown either microbial protein or protein that escapes the small intestine intact, freeing up essential amino acids, and there is considerable evidence for an amino acid absorptive capacity in the hindgut of both avian and mammalian hindgut fermenters. Birds, unlike mammals, do not excrete hyperosmotic urine (i.e. more than five times plasma osmotic concentration). Urine is mixed with digesta rather than directly eliminated, and so the avian gut plays a relatively more important role in water and salt regulation than in mammals. Responses to dehydration and high- and low-salt loads are reviewed. Intestinal absorption of ingested water is modulated to help achieve water balance in one species studied (a nectar-feeding sunbird), the first demonstration of this in any terrestrial vertebrate. In many wild avian species the size and digestive capacity of the GIT is increased or decreased by as much as 50% in response to nutritional challenges such as hyperphagia, food restriction or fasting. The coincident impacts of these changes on osmoregulatory or immune function of the gut are poorly understood. [source] Transepithelial migration of Toxoplasma gondii involves an interaction of intercellular adhesion molecule 1 (ICAM-1) with the parasite adhesin MIC2CELLULAR MICROBIOLOGY, Issue 4 2005Antonio Barragan Summary Toxoplasma gondii crosses non-permissive biological barriers such as the intestine, the blood,brain barrier and the placenta thereby gaining access to tissues where it most commonly causes severe pathology. Herein we show that in the process of migration Toxoplasma initially concentrates around intercellular junctions and probably uses a paracellular pathway to transmigrate across biological barriers. Parasite transmigration required viable and actively motile parasites. Interestingly, the integrity of host cell barriers was not altered during parasite transmigration. As intercellular adhesion molecule 1 (ICAM-1) is upregulated on cellular barriers during Toxoplasma infection, we investigated the role of this receptor in parasite transmigration. Soluble human ICAM-1 and ICAM-1 antibodies inhibited transmigration of parasites across cellular barriers implicating this receptor in the process of transmigration. Furthermore, human ICAM-1 immunoprecipitated the mature form of the parasite adhesin MIC2 present on the parasite surface, indicating that this interaction may contribute to cellular migration. These findings reveal that Toxoplasma exploits the natural cell trafficking pathways in the host to cross cellular barriers and disseminate to deep tissues. [source] Tight junctions, leaky intestines, and pediatric diseasesACTA PAEDIATRICA, Issue 4 2005Z Liu Abstract Background: Tight junctions (TJs) represent the major barrier within the paracellular pathway between intestinal epithelial cells. Disruption of TJs leads to intestinal hyperpermeability (the so-called "leaky gut") and is implicated in the pathogenesis of several acute and chronic pediatric disease entities that are likely to have their origin during infancy. Aim: This review provides an overview of evidence for the role of TJ breakdown in diseases such as systemic inflammatory response syndrome (SIRS), inflammatory bowel disease, type 1 diabetes, allergies, asthma, and autism. Conclusion: A better basic understanding of this structure might lead to prevention or treatment of these diseases using nutritional or other means. [source] Endothelial barriers: from hypothetical pores to membrane proteins*JOURNAL OF ANATOMY, Issue 6 2002J. A. Firth Abstract The anatomical counterpart of the physiologically defined small pore system of capillary endothelia has proved difficult to establish. In non-brain continuous capillaries, the contributions of caveolar and transmembrane pathways are likely to be small and paracellular clefts are probably the dominant routes. Analogy with epithelial paracellular pathways suggests that tight junctions may be the most restrictive elements. However, structural features of tight junction-based models are incompatible with physiological data; it is more likely that the tight junction acts as a shutter limiting the available cleft area. Proposed molecular sieves elsewhere in the paracellular pathway include the glycocalyx and the cadherin-based complexes of the adherens junctions. The molecular architecture of tight junctions and adherens junctions is moderately well defined in terms of molecular species, and there are differences at both sites between the endothelial and epithelial spectra of protein expression. However, definition of the size-restricting pore remains elusive and may require structural biology approaches to the spatial arrangements and interactions of the membrane molecular complexes surrounding the endothelial paracellular clefts. [source] Pores in the Sieve and Channels in the Wall: Control of Paracellular Permeability by Junctional Proteins in Endothelial CellsMICROCIRCULATION, Issue 3 2001GIANFRANCO BAZZONI ABSTRACT Exchange of solutes and ions between the luminal and abluminal compartments of the circulation is critically dependent on the barrier properties of the vascular endothelium. Transport of solutes and fluids occurs along the transcellular and paracellular pathways that are mediated by intracellular vesicles and intercellular junctions, respectively. Although the ability of endothelial cells to dynamically regulate permeability has long been recognized, the precise mechanism and the signaling pathways involved have not been fully elucidated. Finally, current definition of the complex molecular composition of intercellular junctions is expected to explain the difference in permeability between diverse segments of the circulation and possibly to highlight the existence of specific junctional channels. The properties of junctional adhesion molecule-1 (JAM-1) and vascular endothelial cadherin (VE-cadherin), two transmembrane components of interendothelial junctions, are described in detail. [source] MECHANISMS MEDIATING PRESSURE NATRIURESIS: WHAT WE KNOW and WHAT WE NEED TO FIND OUTCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2005Roger G Evans SUMMARY 1.,It is well established that pressure natriuresis plays a key role in long-term blood pressure regulation, but our understanding of the mechanisms underlying this process is incomplete. 2.,Pressure natriuresis is chiefly mediated by inhibition of tubular sodium reabsorption, because both total renal blood flow and glomerular filtration rate are efficiently autoregulated. Inhibition of active sodium transport within both the proximal and distal tubules likely makes a contribution. Increased renal interstitial hydrostatic pressure (RIHP) likely inhibits sodium reabsorption by altering passive diffusion through paracellular pathways in ,leaky' tubular elements. 3.,Nitric oxide and products of cytochrome P450-dependent arachidonic acid metabolism are key signalling mechanisms in pressure natriuresis, although their precise roles remain to be determined. 4.,The key unresolved question is, how is increased renal artery pressure ,sensed' by the kidney? One proposal rests on the notion that blood flow in the renal medulla is poorly autoregulated, so that increased renal artery pressure leads to increased renal medullary blood flow (MBF), which, in turn, leads to increased RIHP. An alternative proposal is that the process of autoregulation of renal blood flow leads to increased shear stress in the preglomerular vasculature and, so, release of nitric oxide and perhaps products of cytochrome P450-dependent arachidonic acid metabolism, which, in turn, drive the cascade of events that inhibit sodium reabsorption. 5.,Central to the arguments underlying these opposing hypotheses is the extent to which MBF is autoregulated. This remains highly controversial, largely because of the limitations of presently available methods for measurement of MBF. [source] | |||||||||||||