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PubMed2005

Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo.

Enteropathogenic Escherichia coli (EPEC) infection disrupts tight junctions (TJs) and perturbs intestinal barrier function in vitro. E. coli secreted protein F (EspF) is, in large part, responsible for these physiological and morphological alterations. We recently reported that the C57BL/6J mouse is a valid in vivo model of EPEC infection as EPEC colonizes the intestinal epithelium and effaces microvilli. Our current aim was to examine the effects of EPEC on TJ structure and barrier function of the mouse intestine and to determine the role of EspF in vivo. C57BL/6J mice were gavaged with approximately 2 x 10(8) EPEC organisms or PBS. At 1 or 5 days postinfection, mice were killed and ileal and colonic tissue was mounted in Ussing chambers to determine barrier function (measured as transepithelial resistance) and short circuit current. TJ structure was analyzed by immunofluorescence microscopy. Wild-type (WT) EPEC significantly diminished the barrier function of ileal and colonic mucosa at 1 and 5 days postinfection. Deficits in barrier function correlated with redistribution of occludin in both tissues. Infection with an EPEC strain deficient of EspF (delta espF) had no effect on barrier function at 1 day postinfection. Furthermore, delta espF had no effect on ileal TJ morphology and minor alterations of colonic TJ morphology at 1 day postinfection. In contrast, at 5 days postinfection, WT EPEC and delta espF had similar effects on barrier function and occludin localization. In both cases this was associated with immune activation, as demonstrated by increased mucosal tumor necrosis factor-alpha levels 5 days postinfection. In conclusion, these data demonstrate that WT EPEC infection of 6-8-week-old C57BL/6J mice (1) significantly decreases barrier function in the ileum and colon (2) redistributes occludin in the ileum and colon and (3) is dependent upon EspF to induce TJ barrier defects at early, but not late, times postinfection.

Animals↗
PubMed2026

Probiotic-derived extracellular vesicles as food-based nanocarriers: Mechanisms, functional applications, and future perspectives in food systems.

Probiotic-derived extracellular vesicles (PDEVs) are a promising type of postbiotic nanoparticle derived by fermentation of probiotics, and have gained growing interest as a potential application in food science and nutrition. These are lipid bilayer vesicles of nanoscale, which are naturally released by probiotic cells and contain a wide variety of bioactive molecules, such as proteins, nucleic acids, and metabolites. Moreover, PDEVs are highly stable, biocompatible, and can be easily engineered to have surfaces with high functionality, which makes them good candidates in functional engineering. In contrast to traditional live probiotics, PDEVs overcome the difficulties of preserving microbial viability during processing and storage, thus providing superior safety, stability, and predictable biological performance. This is a systematic review of the various functions of PDEVs in food systems. We conclude on the processes through which PDEVs control intestinal barrier integrity, alter gut microbiota composition, and alter host immune responses, and their potential to enhance gut health when added to functional foods. In addition to their health-promoting effects, PDEVs have shown significant potential as natural antimicrobial agents to preserve food and as effective nanocarriers of hydrophobic bioactive compounds, including fucoxanthin, to improve their stability, bioavailability, and targeted delivery. Moreover, PDEVs can be used as new regulators of microbial fermentation. However, it should be noted that a lot of the evidence that is available is still preliminary and the effectiveness of these applications in real food-processing and storage conditions has not been fully proven. Although they have potential, there are a number of challenges that still hinder the widespread use of PDEVs in the food industry. These involve the creation of scalable and cost-effective production processes, batch-to-batch consistency, vesicle stability in a variety of food matrices, and regulatory and safety considerations. Other emerging engineering approaches, such as surface functionalization and cargo loading, are also discussed in this review and could further increase the specificity, functionality, and application versatility of PDEVs in food systems. Moving forward, the incorporation of PDEVs into the next generation functional foods, novel food preservation methods, and customized nutrition plans should be prioritized in future studies. Further developments in these fields can make PDEVs useful platforms at the interface of food microbiology, nanotechnology, and human health.

Probiotics↗
PubMed2000

Evidence for cytochrome P4501A2-mediated protein covalent binding of thiabendazole and for its passive intestinal transport: use of human and rabbit derived cells.

Thiabendazole (TBZ), an anthelmintic and fungicide benzimidazole, was recently demonstrated to be extensively metabolized by cytochrome P450 (CYP) 1A2 in man and rabbit, yielding 5-hydroxythiabendazole (5OH-TBZ), the major metabolite furtherly conjugated, and two minor unidentified metabolites (M1 and M2). In this study, exposure of rabbit and human cells to 14C-TBZ was also shown to be associated with the appearance of radioactivity irreversibly bound to proteins. The nature of CYP isoforms involved in this covalent binding was investigated by using cultured rabbit hepatocytes treated or not with various CYP inducers (CYP1A1/2 by beta-naphthoflavone, CYP2B4 by phenobarbital, CYP3A6 by rifampicine, CYP4A by clofibrate) and human liver and bronchial CYP-expressing cells. The covalent binding to proteins was particularly increased in beta-naphthoflavone-treated rabbit cells (2- to 4-fold over control) and human cells expressing CYP1A2 (22- to 42-fold over control). Thus, CYP1A2 is a major isoenzyme involved in the formation of TBZ-derived residues bound to protein. Furthermore, according to the good correlation between covalent binding and M1 or 5OH-TBZ production, TBZ would be firstly metabolized to 5OH-TBZ and subsequently converted to a chemically reactive metabolic intermediate binding to proteins. This metabolic activation could take place preferentially in liver and lung, the main biotransformation organs, rather than in intestines where TBZ was shown to be not metabolized. Moreover, TBZ was rapidly transported by passive diffusion through the human intestinal cells by comparison with the protein-bound residues which were not able to cross the intestinal barrier. Consequently, the absence of toxicity measured in intestines could be related to the low degree of TBZ metabolism and the lack of absorption of protein adducts. Nevertheless, caution is necessary in the use of TBZ concurrently with other drugs able to regulate CYP1A2, particularly in respect to liver and lung tissues, recognised as sites of covalent-binding.

Animals↗
PubMed1999

[Parenteral and enteral nutrition in palliative medicine].

Artificial nutritional support does not alter the natural course in patients with malignant disease. The outcome of these patients is mainly determined by the type and stage of the underlying tumor. Progress of the underlying disease is often paralleled by malnutrition which in turn facilitates complications and may reduce survival and quality of life. Nutritional support can be applied to maintain body weight, immune function and quality of life. Enteral nutrition can be applied with a functioning gastrointestinal tract and has been proven to be superior compared to parenteral nutrition. Maintenance of intestinal mucosal function due to enteral substrate application prevents disruption of intestinal barrier function as well as the overgrowth of intestinal microorganisms. Using a step-by-step approach dietetic counselling in combination with augmented oral caloric intake should be the first measure. The next step to take is nutritional support by enteral tube feeding using formula diets. Parenteral feeding should only be used if other options to support caloric intake have failed.

Enteral Nutrition↗
PubMed2004

Genetic aspects of intestinal permeability in inflammatory bowel disease.

There is a long-standing belief that disruption of the intestinal barrier function may lead to systemic and local intestinal disease. The role of increased intestinal permeability in Crohn's disease is reviewed here. What is not in doubt is that intestinal permeability in patients with Crohn's disease is increased proportional to disease activity; it can be used to predict clinical relapse of disease and prognosis; and a small proportion of first-degree relatives have increased intestinal permeability. This last finding has been subject to much speculation. In particular it has been suggested that it represents a genetically determined abnormality. If so it might play an important pathogenic process in the disease. However this permeability change in relatives does not conform to a classical inheritance pattern and in some studies it is found in the patients' spouses. This suggests an environmental cause for the changes. However proponents of an environmental factor have been singularly inactive in attempting to identify this agent(s). In view of recent research it seems likely that the increased intestinal permeability in relatives of Crohn's patients may be secondary to sub-clinical intestinal inflammation. This inflammation conforms to an inherited additive trait. The genetic basis for this inflammation is being studied.

Crohn Disease↗
PubMed2000

[Protection of the mucosal barrier by nutritional strategies. What are the therapeutic options?].

The dysfunction of intestinal barrier allows the translocation of both endotoxin and whole bacterial organisms. It plays an important role in the development of multiple organ failure (MOF). The mucosa ia one component of this barrier. Trauma, atrophy and the "systemic inflammatory response syndrome" increase gastrointestinal permeability. These abnormalities may contribute to the pathophysiology of sepsis. Malnutrition per se compromises the gut's barrier function. Maintenance of gastrointestinal blood flow may be facilitated by (glutamine-enriched?) enteral diets. The most important conclusions of the majority of controlled trials support the concept of the very early enteral nutrition (within 24 hours after trauma): the outcome of seriously ill patients is improved, the rate of complications and infections is reduced. Gastrointestinal motility disorders may interfere with the initiation and tolerance of early enteral nutrition. They may be managed by prokinetic agents (cisapride, erythromycin) or by bypassing the stomach with a nasoenteric tube.

Gastrointestinal Diseases↗
PubMed2000

The key role of Pseudomonas aeruginosa PA-I lectin on experimental gut-derived sepsis.

OBJECTIVE: To examine the effect of Pseudomonas aeruginosa on intestinal barrier function and its lethal potential when introduced into the intestinal tract of mice. SUMMARY BACKGROUND DATA: The mere presence of P. aeruginosa in the intestinal tract of critically ill patients is associated with a threefold increase in death compared with matched cohorts without this pathogen. Whether this effect is a cause or a consequence of the critically ill state has not been previously addressed. METHODS: Transepithelial electrical resistance, a measure of tight junction permeability, was evaluated in Caco-2 intestinal epithelial cells cells apically inoculated with live P. aeruginosa, exotoxin A, or purified PA-I lectin, an adhesin of P. aeruginosa. Lethality studies to P. aeruginosa were carried out in mice undergoing 30% surgical hepatectomy by injecting the bacteria or its various components directly into the cecum. RESULTS: Only cells exposed to P. aeruginosa or its PA-I lectin developed alterations in barrier function. P. aeruginosa or the combination of PA-I and exotoxin A was lethal to mice when injected into the cecum after partial hepatectomy. Alterations in epithelial barrier function and death in mice were prevented when Pseudomonas was pretreated with N-acetyl D-galactosamine (GalNAc), a binder of PA-I. CONCLUSIONS: P. aeruginosa may act as a pathogen in the gastrointestinal tract, resulting in altered epithelial barrier function and death in a susceptible host. The PA-I lectin of P. aeruginosa may play a key role in its pathogenicity to the intestinal epithelium by inducing a permeability defect to its cytotoxic exoproducts such as exotoxin A.

Adhesins, Bacterial↗
PubMed2005

The pivotal role of tumor necrosis factor-alpha in signaling apoptosis in intestinal epithelial cells under shock conditions.

BACKGROUND: Apoptosis is essential for the regulation of cell number and function of intestinal epithelial cells but may contribute to intestinal barrier failure after shock and other low-flow conditions to the gut. METHODS: Caco2 intestinal cell monolayers were challenged with recombinant tumor necrosis factor (TNF). In a second group of experiments, Caco2 cells were exposed to bacteria and/or hypoxia followed by reoxygenation. Apoptosis was detected using annexin-V propidium-iodide staining. Cell culture supernatants were also obtained in the second group of experiments and TNF levels quantitated. Monolayer integrity was assessed by measurement of paracellular permeability and transepithelial electrical resistance. RESULTS: Apical but not basal recombinant TNF increased Caco2 apoptosis. Exposure to either bacteria alone or hypoxia/reoxygenation alone did not increase apoptosis; however, the combined insults significantly increased apoptosis. The increased apoptosis occurred in a delayed fashion in both groups. TNF was released in a polar fashion, and the greatest levels were noted after exposure to both bacteria and hypoxia-reoxygenation. There was also an increase in paracellular permeability in this group; however, no change in transepithelial electrical resistance was noted. The effects on apoptosis and permeability were abrogated by anti-TNF antibodies. CONCLUSION: Intestinal epithelial cell apoptosis contributes to barrier failure after shock conditions and is related to augmented TNF release.

Apoptosis↗
PubMed2006

Protective effects of hyperoxygenated solution preconditioning on intestinal ischemia-reperfusion injury in rabbits.

BACKGROUND: The aim of this study was to investigate the protective effects of hyperoxygenated solution (HOS) preconditioning on intestinal ischemia-reperfusion (IR) injury in rabbits. MATERIALS AND METHODS: Thirty-two rabbits were randomly divided into four groups as follows: (1) control group in which sham operation was performed (Sham group); (2) sham operation and HOS treatment group (sham+H group); (3) ischemia-reperfusion group (IR group); (4) ischemia-reperfusion and HOS treatment group (H group). Intestinal IR model was produced by clamping superior mesenteric artery with an atraumatic vascular clamp for 1 h, followed by reperfusion for 2 h. Animals in H group received intravenous HOS infusion (20 mL/kg) every day for 5 days before ischemia-reperfusion; animals in the sham+H group received the same amount of HOS before sham operation, and animals in IR group received the same amount of normal saline in the same way. At the end of reperfusion, histopathological changes of intestine were observed, and malondialdehyde (MDA) levels, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities in intestinal tissues were also detected. Intestinal barrier function was assessed by blood d-lactate levels and bacterial translocation (BT). RESULTS: The H group showed significantly lower MDA levels and higher activities of SOD, CAT, and GSH-Px in the intestinal tissue compared with the IR group. Furthermore, the mean d-lactate levels and incidence of BT in the H group were significantly lower than those in the IR group. Histopathological analysis also indicated that there were significant histological improvements in the H group compared with the IR group. CONCLUSIONS: HOS preconditioning at an appropriate dose ameliorates the deleterious changes in intestinal mucosal injury and barrier function associated with IR by effectively preventing a decrease in the intestinal antioxidant defense system, which is another simple and effective measure to protect intestine from IR injury.

Animals↗
PubMed1998

Effect of a platelet-activating factor antagonist on pancreatitis-associated gut barrier dysfunction in rats.

Platelet-activating factor (PAF) may play a critical and primary role in the pathogenesis of acute pancreatitis and pancreatitis-associated distant organ injury. The present study evaluated the effect of a PAF antagonist, lexipafant (an (S)-4-methyl-2[methyl-imidazo[4,5-c]pyridin-1-ylmethyl)-benzene sulphonyl]-amino]pentanoic acid ethyl ester, BB-882; British Biotech Ltd.), on the potential prevention of gut barrier dysfunction, by measuring gut origin sepsis, bidirectional permeability of the intestinal barrier, and pancreatic capillary endothelial barrier integrity, in acute pancreatitis induced by intraductal infusion of 5% sodium taurodeoxycholate. Pancreatic endothelial permeability significantly increased in animals with acute pancreatitis, whereas pretreatment with lexipafant had a preventive effect (p < 0.05 vs. pancreatitis with saline). Similarly, alterations noted in hematocrit and plasma levels of lipase and calcium were counteracted by the PAF antagonist. It also prevented the increase in albumin leakage from blood to the mucosal interstitium and from blood to the intestinal lumen in acute pancreatitis. Albumin passage from the gut lumen to blood in animals with pancreatitis pretreated with saline increased from 3 h and on, and lexipafant prevented alterations in mucosal epithelial permeability. Bacterial translocation was commonly seen in pancreatitis, whereas only a few positive cultures were observed in pancreatitis animals given lexipafant. Microthrombosis in intestinal villi seemed less frequent after lexipafant pretreatment. We conclude that (a) PAF may play a role in the pathogenesis of pancreatitis-associated intestinal dysfunction, (b) PAF may be involved in the development of distant organ dysfunction by triggering endothelial barrier dysfunction, and (c) PAF antagonists may provide potential agents for preventing pancreatitis-associated gut barrier dysfunction.

Acute Disease↗
PubMed2006

The roles of bacteria and TLR4 in rat and murine models of necrotizing enterocolitis.

Bacteria are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC), but it is unknown whether their interaction with the epithelium can participate in the initiation of mucosal injury or they can act only following translocation across a damaged intestinal barrier. Our aims were to determine whether bacteria and intestinal epithelial TLR4 play roles in a well-established neonatal rat model and a novel neonatal murine model of NEC. Neonatal rats, C57BL/6J, C3HeB/FeJ (TLR4 wild type), and C3H/HeJ (TLR4 mutant) mice were delivered by Cesarean section and were subjected to formula feeding and cold asphyxia stress or were delivered naturally and were mother-fed. NEC incidence was evaluated by histological scoring, and gene expression was quantified using quantitative real-time PCR from cDNA generated from intestinal total RNA or from RNA obtained by laser capture microdissection. Spontaneous feeding catheter colonization or supplementation of cultured bacterial isolates to formula increased the incidence of experimental NEC. During the first 72 h of life, i.e., the time frame of NEC development in this model, intestinal TLR4 mRNA gradually decreases in mother-fed but increases in formula feeding and cold asphyxia stress, correlating with induced inducible NO synthase. TLR4, inducible NO synthase, and inflammatory cytokine induction occurred in the intestinal epithelium but not in the submucosa. NEC incidence was diminished in C3H/HeJ mice, compared with C3HeB/FeJ mice. In summary, bacteria and TLR4 play significant roles in experimental NEC, likely via an interaction of intraluminal bacteria and aberrantly overexpressed TLR4 in enterocytes.

Animal Feed↗
PubMed2000

[Bacterial translocation from the gastrointestinal tract: catalyst of multiple organ dysfunction syndrome].

The abnormal colonization of gastrointestinal tract (GIT), the loss of the intestinal barrier function, the bacterial translocation (BT) are signs of intestinal insufficiency which are supposed to be involved in the pathogenesis of MODS. This worsens the condition or leads to lethal outcome in patients after major abdominal surgery in ICU. The goal of this investigation was to consider the scientific and clinical evidence for the BT role in the pathogenesis of MODS and to present evidence about the advantages and the efficiency of antibiotic combination Amikacin plus Clindamycin as a new therapeutic strategy for the improvement of the outcome in patients with MODS and sepsis. To that purpose patients with diffuse peritonitis of different origin were analyzed. After surgery some patients were left with laparostomy. This gave the possibility for revisions and lavages of the abdominal cavity and for taking material for microbiological analyses. The patients were grouped into two subgroups according to antibiotic treatment: 1st group--combination of usually used antibiotics; 2nd group--Amikacin plus Clindamycin. The second group patients showed good tolerance to this antibiotic combination and good therapeutic effect.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Animal study on radioactive antigenic fractions isolated from V.cholerae. I. The Ch 1 + 2 fraction].

The Ch 1 + 2 fraction has been marked by means of culture of Vibrio cholerae Ogawa HK1 on a synthetic medium containing leucine H3. The antigen distribution has been then studied before and after vaccination with the same non-marked antigen in normal and axenic mice, at the same time by the demonstration of radioactivity and radioimmunofluorescence in intestine, spleen, liver, kidney and thymus. Whichever the administration route, intestine and spleen are first stimulated, then more intensively with the second injection or ingestion. When administrated per os the fraction crosses the intestinal barrier and is fixed on the main lymphoid organs: intestine, spleen, thymus. After ingestion or injection into axenic mice, spleen is the first organ stimulated.

Animals↗
PubMed1990

Bacterial translocation and intestinal atrophy after thermal injury and burn wound sepsis.

Bacterial translocation (BT) occurs after thermal injury in rodents in association with intestinal barrier loss. Infection complicating thermal injury may also affect the intestine producing bowel atrophy. To study these relationships, Wistar rats received either 30% scald followed by wound inoculation with Pseudomonas; 30% scald with pair feeding to infected animals; or sham injury as controls. On days 1, 4, and 7 after injury animals were killed with examination of the bowel and culture of the mesenteric lymph nodes (MLN), livers, spleens, and blood. All burned animals demonstrated BT to the MLN on day 1 after injury, but only burn-infected animals had continued BT on days 4 and 7, with progression of BT to the abdominal organs and blood. Burn injury and infection also resulted in significant atrophy of small bowel mucosa temporally associated with continued BT. Thus injury complicated by infection results in prolonged and enhanced bacterial translocation, perhaps due to failure to maintain the mucosal barrier.

Animals↗
PubMed1993

Nutrition and the gut mucosal barrier.

That the gastrointestinal tract performs important immunologic, metabolic, and barrier functions, in addition to nutrient digestion and absorption, has recently become clear, as have the potential deleterious consequences of loss of mucosal barrier function. Because of the potentially important relationship between nutrition and gut barrier function, this area has received increasing clinical and experimental attention over the past several years. Consequently, this review focuses on how nutrition can modulate the integrity of the gut mucosal barrier. Special attention will be given to the biology of normal intestinal barrier function, as well as to studies investigating the role of nutritionally related variables on the gut mucosal barrier.

Animals↗
PubMed2001

The gut mucosa barrier is preserved during allogeneic, haemopoietic stem cell transplantation with reduced intensity conditioning.

The efficacy of allogeneic, haemopoietic stem cell transplantation (HSCT) is limited by concomitant toxicity. This has led to the development of less toxic, reduced intensity conditioning (RIC) protocols, whose therapeutic benefit is largely related to an associated, immunity-mediated graft-versus-malignancy effect rather than by the cytotoxic treatment itself. Murine HSCT models suggests that acute graft-versus-host disease (GVHD) increases with the intensification of the conditioning regimen mediated by loss of integrity of the gut mucosa barrier. The present study was undertaken to investigate gastro-intestinal (GI) permeability during allogeneic HSCT with RIC. In 17 patients (myeloablative conditioning in nine, RIC in eight), intestinal permeability was assessed by a (51)Cr-EDTA absorption test before the start of cytotoxic treatment the day before stem cell infusion (day -1) and 4, 7 and 14 days after stem cell infusion. Patients receiving RIC did not develop any significant increase in intestinal permeability during the transplantation course but in myeloablatively conditioned patients there was a significant increase in intestinal permeability the day before the stem cell infusion (P < 0.005), on day 4 (P < 0.005), on day 7 (P < 0.01) and on day 14 (P < 0.005) after stem cell infusion, compared with the baseline. Myeloablative conditioning also revealed increased intestinal permeability on day 7 compared with the RIC (P < 0.05). The finding of preserved intestinal-barrier function during allogeneic HSCT with RIC is discussed, with reference to the hypothesis that GI tract damage may be an important initiating event of GVHD.

Adult↗
PubMed1990

A clinical and endocrine study on the effect of orally administered bacterial endotoxin in adult pigs and goats.

Endotoxin of Gram-negative bacteria was orally administered in 5 female pigs and 8 male goats. Two of the gilts were pregnant. A solution of lipopolysaccharide (LPS) of Enterobacter agglomerans was mixed into the feed ration of the pigs (40 mg/animal), and given by gastric tube into the rumen of the goats (1-20 mg/animal). Jugular venous blood was collected and clinical signs, rectal temperature and WBC counts were recorded for 12-24 hours. Plasma concentrations of the major plasma metabolite of PGF2 alpha, 15-keto-13,14-dihydro-PGF2 alpha were determined in both species, progesterone concentration only in pigs. The pigs showed slight to severe signs of endotoxemia. Increases in rectal temperature and levels of the PGF2 alpha metabolite occurred in 3 gilts. Progesterone level and the total WBC counts remained unchanged. Differential counts followed irregular patterns mostly within the normal range. The goats showed slight signs of discomfort. Temperature increased in one animal. No other parameters were altered after the intake of LPS. The observations in pigs indicate that endotoxin either penetrated the intestinal barrier causing systemic endotoxemia or induced inflammatory reactions in the intestine activating inflammatory mediators.

Administration, Oral↗
PubMed2005

Epithelial barrier function in vivo is sustained despite gaps in epithelial layers.

BACKGROUND & AIMS: Epithelial cells of the small intestine migrate to the tip of the villus at which they are shed. It is not understood how the intestinal barrier is maintained during this high cell turnover. The aim of this study was to use high-resolution in vivo light microscopy to investigate the mechanism of epithelial shedding and the site of the permeability barrier during cell shedding. METHODS: A laparotomy was performed on anesthetized mice, and a segment of small intestine was opened. The exposed epithelial surface of the intestine was imaged by multiphoton microscopy. Nuclei, cytosol, and cell membranes were imaged using the dyes Hoescht 33258, BCECF, a transgenically expressed fluorescent protein, and the membrane dye DiI. The fluorescent caspase substrate PhiPhiLux was used to detect apoptosis. RESULTS: In the epithelial monolayer, gaps were observed that lacked nuclei or cytosol but appeared to be filled with an impermeable substance. Studies with membrane impermeant fluorophores (Lucifer Yellow and Alexa-dextran) showed that the impermeable substance completely fills the void left by the absent cell. Only a fraction of gaps have either ZO-1 staining or cytoplasmic extensions from neighboring cells at the basal pole. Time-lapse studies reveal that cell shedding results in genesis of a gap and that shedding usually occurs prior to detectable cellular activation of caspase 3 or nuclear condensation. CONCLUSIONS: Results suggest that epithelial barrier function is sustained at the apical pole of the epithelial layer, despite discontinuities in the cellular layer.

Animals↗