Food Proteins and Gut Mucosal Barrier. II. Differential Interaction of Cow's Milk Proteins with the Mucous Coat and the Surface Membrane of Adult and Immature Rat Jejunum

Stern, Martin; Pang, K Y; Walker, W. Allan

doi:10.1203/00006450-198412000-00005

Cited by 48 publications

(22 citation statements)

References 22 publications

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“…Crypt IECs affected by CD inflammation show similar trafficking of OVA and expression of MHC II compared with villus IECs. Because a distinct function of immature IECs in antigen uptake has been reported, antigen presentation by crypt IECs might specifically contribute to the inflammatory processes in CD ileitis (37). Furthermore, we suggest that the IECs' function as APCs might crucially depend on antigen processing properties and the differential involvement of inflammation-related costimulatory molecules such as B-7 proteins (2,16,28).…”

Section: Discussionmentioning

confidence: 92%

Luminal antigens access late endosomes of intestinal epithelial cells enriched in MHC I and MHC II molecules: in vivo study in Crohn's ileitis

Hundorfean¹,

Zimmer²,

Ströbel³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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In contrast to healthy conditions, intestinal epithelial cells (IECs) stimulate proinflammatory CD4+ and CD8+ T cells during Crohn's disease (CD). The underlying regulatory mechanisms remain unknown. Here we investigated the epithelial expression of major histocompatibility complex (MHC) I and MHC II and its interference with endocytic pathways, in vivo. During ileoscopy, ovalbumin (OVA) was sprayed onto ileal mucosa of CD patients (ileitis and remission) and controls. The epithelial traffic of OVA and MHC I/II pathways were studied in biopsies using fluorescence and electron microscopy. We found MHC I and MHC II to accumulate within multivesicular late endosomes (MVLE) of IECs. Faint labeling for these molecules was seen in early endosomes and lysosomes. MVLE were entered by OVA 10 min after exposure. Exosomes carrying MHC I, MHC II, and OVA were detected in intercellular spaces of the epithelium. OVA trafficking and labeling patterns for MHC I and MHC II in IECs showed no differences between CD patients and controls. Independent of inflammatory stimuli, MHC I and MHC II pathways intersect MVLE in IECs, which were efficiently targeted by luminal antigens. Similar to MHC II-enriched compartments in professional antigen presenting cells, these MVLE might be critically involved in MHC I- and MHC II-related antigen processing in IECs and the source of epithelial-released exosomes. The access of luminal antigens to MHC I in MVLE might indicate that the presentation of exogenous antigens by IECs must not be restricted to MHC II but might also occur as "cross-presentation" via MHC I to CD8+ T cells.

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Section: Discussionmentioning

confidence: 92%

Luminal antigens access late endosomes of intestinal epithelial cells enriched in MHC I and MHC II molecules: in vivo study in Crohn's ileitis

Hundorfean¹,

Zimmer²,

Ströbel³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…This could also explain why antigen uptake is increased in these cells, because immature enterocytes are known to be more susceptible to antigen uptake than fully differentiated cells. 33 The most likely reason why RACE cells have not been previously described by others is because of the lack of a suitable experimental design that combines morphological and functional assessments in the same setting. Our approach using immunoelectron microscopy could unequivocally unravel the distinct ultrastructural characteristics of RACE cells and highlight an efficient uptake of luminal antigens into endocytic compartments and finally into the cytosol.…”

Section: Discussionmentioning

confidence: 99%

Antigen Transport and Cytoskeletal Characteristics of a Distinct Enterocyte Population in Inflammatory Bowel Diseases

Kersting

Bruewer

Schuermann

et al. 2004

The American Journal of Pathology

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Intestinal antigen uptake is enhanced in inflammatory bowel disease. We analyzed transcellular transport routes of antigens in different compartments of normal enterocytes and atypical intestinal epithelial cells called "rapid antigen uptake into the cytosol enterocytes" (RACE cells). These cells constitute a recently described population of enterocyte-derived cells, which are increased in inflammatory bowel disease. Mucosa of freshly resected specimens were incubated with the antigens ovalbumin or horseradish peroxidase. Ultrastructural labeling patterns of differentiation-dependent proteins, the brush-border enzyme sucrase-isomaltase and the cytoskeleton proteins villin and actin, were determined in enterocytes. Apoptosis was investigated biochemically and ultrastructurally by cleavage of caspase-3. Both antigens were transported to late endosomes and to trans-Golgi vesicles of enterocytes in inflammatory bowel disease and control specimens. Quantitative evaluation revealed a significantly increased transepithelial antigen transport in both compartments of RACE relative to normal enterocytes. Labeling densities for sucrase-isomaltase, villin, and actin were decreased in RACE relative to normal enterocytes. Caspase-3 was not increased in RACE cells relative to controls. RACE cells are characterized by increased antigen transport to late endosomes and the trans-Golgi network, a disassembled cytoskeleton and lower concentrations of proteins that are markers of cell differentiation. 2-4We have recently shown that the antigens ovalbumin (OVA) and horseradish peroxidase (HRP) are taken up at the apical membrane in CD, UC, and healthy controls (HCs) and are detected in vacuoles of enterocytes and the paracellular space within minutes after administration. Both antigens were not localized within the cytosol of normal enterocytes (NE cells). In addition to ultrastructurally NEs, we demonstrated an increased number of atypical enterocytes with a decreased concentration of mitochondrial ATP synthase, shortened microvilli, an electron lucent cytosol, and high amounts of OVA or HRP in the cytosol of both CD and UC enterocytes relative to patients without inflammatory disorders as well as patients with diverticulitis, that show similar amounts of these enterocytes. These atypical enterocytes are called "rapid antigen uptake into the cytosol enterocytes" (RACE cells). Moreover the presence of RACE cells correlated with the degree of mucosal inflammation in CD and UC. 5 However, the functional significance, differentiation, origin, and fate of RACE cells are still unclear. In particular, the transport pathway of antigens through endocytic cell compartments and the mechanism of the rapid cytosolic antigen uptake of RACE cells have not yet been elucidated. This study has been conducted to characterize transepithelial antigen transport within RACE cells relative to NEs using bowel specimens of patients with CD or UC. To investigate whether cytosolic arrival of antigens follows enhanced endocytosis and intracellular release of a...

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“…This is one of the underlying mechanisms inducing food protein intolerance. Likewise, it has been documented that young rats with immature intestinal functions and abnormal mucosal permeability to macromolecules are confronted with more intact food antigens that bind to the enterocyte surface (12,13). In young suckling rats, intact cow's milk proteins are degraded much less than in older rats (13), resulting in increased binding of intact cow's milk antigens to BBM (14).…”

mentioning

confidence: 99%

Saccharomyces boulardii Enhances N-Terminal Peptide Hydrolysis in Suckling Rat Small Intestine by Endoluminal Release of a Zinc-Binding Metalloprotease

et al. 2002

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Saccharomyces boulardii (S. boulardii), a biotherapeutic agent effective in acute and chronic enterocolopathies, produces trophic intestinal effects at least in part mediated by the endoluminal release of polyamines. However, the effects of the yeast on peptide hydrolysis have not yet been studied. The objectives of this study were to assess in suckling rats the endoluminal and mucosal aminopeptidase activities in response to S. boulardii treatment and to analyze their related mechanisms. Peptidase activities were assayed on yeast cells by using several L-amino acid-p-nitroanilide substrates in the pH range of 2 to 10. A marked hydrolytic activity was found for L-leucine-p-nitroanilide that peaked at pH ϭ 8 (K m ϭ 0.334 mM, V max ϭ 44.7 mol·min Ϫ1 ·g -1 protein). N-terminal peptide hydrolysis was confirmed using as substrate L-Leu-Gly-Gly (K m ϭ 4.71 mM, V max ϭ 18.08 mol·min Ϫ1 ·g -1 protein). Enzyme reactions were inhibited in the presence of 1 mM Zn 2ϩ . Oral treatment of sucklings with S. boulardii significantly enhanced jejunal and ileal mucosal leucine-aminopeptidase activities by 24 and 34%, respectively, over controls. In concordance, aminopeptidase activity was enhanced in jejunal and ileal endoluminal fluid samples by 47 and 105%, respectively. By use of an IgG-purified antibody raised against the zinc-binding domain common to metalloproteases, the yeast aminopeptidase was immunoprecipitated and detected as an heteromeric enzyme of 108 and 87-kD subunits. S. boulardii, when given orally to suckling rats, is able to significantly enhance hydrolysis of N-terminal oligopeptides in both endoluminal fluid and intestinal mucosa by the endoluminal release of a leucine aminopeptidase that appears to be a zinc-binding metalloprotease belonging to the M1 family of peptidases. Saccharomyces boulardii (S. boulardii) is a nonpathogenic yeast exerting therapeutic properties in acute and chronic enterocolopathies, antibiotic-associated diarrheas, and enterotoxigenic Clostridium difficile overgrowth (1-4).In human volunteers (5, 6) and in growing rats (5), several studies have documented that oral treatment with a lyophilized preparation of S. boulardii produces trophic intestinal effects including increases in the specific and total activities of brushborder membrane (BBM) enzymes (5), enhanced secretion of s-IgA in intestinal fluid (7), and enhanced production of the receptor for polymeric Ig in villus and crypt cells (7). In addition, after oral treatment of rats with S. boulardii, there is a marked stimulation of sodium-dependent D-glucose uptake into BBM vesicles with a corresponding accumulation of the BBM sodium D-glucose cotransporter-1 (SGLT-1, 75 kD) (8). These trophic effects are, at least in part, mediated by endoluminal release of polyamines, as yeast cells contain substantial amounts of putrescine, spermidine, and spermine (9, 10). In addition, polyamine concentrations in mucosa and endoluminal fluid were found to be increased in proportion to the amount of spermine and spermidine supplied by the yeast ...

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Food Proteins and Gut Mucosal Barrier. II. Differential Interaction of Cow's Milk Proteins with the Mucous Coat and the Surface Membrane of Adult and Immature Rat Jejunum

Cited by 48 publications

References 22 publications

Luminal antigens access late endosomes of intestinal epithelial cells enriched in MHC I and MHC II molecules: in vivo study in Crohn's ileitis

Luminal antigens access late endosomes of intestinal epithelial cells enriched in MHC I and MHC II molecules: in vivo study in Crohn's ileitis

Antigen Transport and Cytoskeletal Characteristics of a Distinct Enterocyte Population in Inflammatory Bowel Diseases

Saccharomyces boulardii Enhances N-Terminal Peptide Hydrolysis in Suckling Rat Small Intestine by Endoluminal Release of a Zinc-Binding Metalloprotease

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