Chronic Psychological Stress in Rats Induces Intestinal Sensitization to Luminal Antigens
2006; Elsevier BV; Volume: 168; Issue: 1 Linguagem: Inglês
10.2353/ajpath.2006.050575
ISSN1525-2191
AutoresPing‐Chang Yang, Jennifer Jury, Johan D. Söderholm, Philip M. Sherman, Derek M. McKay, Mary H. Perdue,
Tópico(s)Stress Responses and Cortisol
ResumoThere is increasing evidence that stress plays a role in the pathophysiology of chronic intestinal disorders, but the mechanisms remain unclear. Previous studies in rats have revealed that stress decreases gut barrier function and allows excessive uptake of luminal material. Here, we investigated whether chronic psychological stress acts to induce sensitization of intestinal tissues to oral antigens. Rats were subjected to 1 hour per day of water avoidance stress or sham stress daily for 10 days, and horseradish peroxidase (HRP) was delivered by gavage on day 5. Studies to determine sensitization were conducted on day 20. All stressed rats developed HRP-specific IgE antibodies, antigen-induced intestinal secretion, and increased numbers of inflammatory cells in gut mucosa. Luminal HRP was absorbed more readily by enterocytes of stressed animals. In addition, stressed rats had increased expression of interleukin-4 and decreased expression of interferon-γ in gut mucosa, a cytokine profile that is typical of allergic conditions. Treatment of stressed rats with an antagonist to corticotropin-releasing hormone (previously shown to inhibit stress-enhanced gut permeability) eliminated the manifestations of intestinal hypersensitivity. Our results indicate that the presence of oral antigen during chronic psychological stress alters the immune response (to sensitization rather than oral tolerance) and causes subsequent antigen-induced gut pathophysiology. There is increasing evidence that stress plays a role in the pathophysiology of chronic intestinal disorders, but the mechanisms remain unclear. Previous studies in rats have revealed that stress decreases gut barrier function and allows excessive uptake of luminal material. Here, we investigated whether chronic psychological stress acts to induce sensitization of intestinal tissues to oral antigens. Rats were subjected to 1 hour per day of water avoidance stress or sham stress daily for 10 days, and horseradish peroxidase (HRP) was delivered by gavage on day 5. Studies to determine sensitization were conducted on day 20. All stressed rats developed HRP-specific IgE antibodies, antigen-induced intestinal secretion, and increased numbers of inflammatory cells in gut mucosa. Luminal HRP was absorbed more readily by enterocytes of stressed animals. In addition, stressed rats had increased expression of interleukin-4 and decreased expression of interferon-γ in gut mucosa, a cytokine profile that is typical of allergic conditions. Treatment of stressed rats with an antagonist to corticotropin-releasing hormone (previously shown to inhibit stress-enhanced gut permeability) eliminated the manifestations of intestinal hypersensitivity. Our results indicate that the presence of oral antigen during chronic psychological stress alters the immune response (to sensitization rather than oral tolerance) and causes subsequent antigen-induced gut pathophysiology. Related Commentary on page 3 A number of publications1Collins SM Stress and the gastrointestinal tract IV. Modulation of intestinal inflammation by stress: basic mechanisms and clinical relevance.Am J Physiol. 2001; 280: G315-G318Google Scholar, 2Monnikes H Tebbe JJ Hildebrandt M Arck P Osmanoglou E Rose M Klapp B Wiedenmann B Heymann-Monnikes I Role of stress in functional gastrointestinal disorders. Evidence for stress-induced alterations in gastrointestinal motility and sensitivity.Dig Dis. 2001; 19: 201-211Crossref PubMed Scopus (224) Google Scholar, 3Hart A Kamm MA Mechanisms of initiation and perpetuation of gut inflammation by stress.Aliment Pharmacol Ther. 2002; 16: 2017-2028Crossref PubMed Scopus (114) Google Scholar, 4Kelsay K Psychological aspects of food allergy.Curr Allergy Asthma Rep. 2003; 3: 41-46Crossref PubMed Scopus (29) Google Scholar in recent years indicate that stress plays a role in gastrointestinal pathophysiology in conditions such as inflammatory bowel disease, irritable bowel syndrome (IBS), and food allergies. In inflammatory bowel disease and perhaps IBS, there is evidence that intestinal tissues may become sensitized to a luminal antigen and that subsequent encounter with the antigen initiates an inflammatory response that is involved in the pathophysiology of disease.5Guarner F Casellas F Borruel N Antolin M Videla S Vilaseca J Malagelada JR Role of microecology in chronic inflammatory bowel diseases.Eur J Clin Nutr. 2002; 56: S34-S38Crossref PubMed Scopus (52) Google Scholar, 6Landers CJ Cohavy O Misra R Yang H Lin YC Braun J Targan SR Selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto- and microbial antigens.Gastroenterology. 2002; 123: 689-699Abstract Full Text Full Text PDF PubMed Scopus (374) Google Scholar, 7Van Den Bogaerde J Cahill J Emmanuel AV Vaizey CJ Talbot IC Knight SC Kamm MA Gut mucosal response to food antigens in Crohn's disease.Aliment Pharmacol Ther. 2002; 16: 1903-1915Crossref PubMed Scopus (45) Google Scholar, 8Chadwick VS Chen W Shu D Paulus B Bethwaite P Tie A Wilson I Activation of the mucosal immune system in irritable bowel syndrome.Gastroenterology. 2002; 122: 1778-1783Abstract Full Text Full Text PDF PubMed Scopus (711) Google Scholar, 9Zar S Kumar D Benson MJ Food hypersensitivity and irritable bowel syndrome.Aliment Pharmacol Ther. 2001; 15: 439-449Crossref PubMed Scopus (107) Google Scholar Although this theory remains controversial, it is clear that sensitization of intestinal tissues is a feature of food allergy. There is little information on the relationship between stress and intestinal anaphylaxis, although several reports indicate that psychological stress triggers allergic reactions in other organ systems.10Marshall GD Agarwal SK Stress, immune regulation, and immunity: applications for asthma.Allergy Asthma Proc. 2000; 21: 241-246Crossref PubMed Scopus (118) Google Scholar, 11Anderzen I Arnetz BB Soderstrom T Soderman E Stress and sensitization in children: a controlled prospective psychophysiological study of children exposed to international relocation.J Psychosom Res. 1997; 43: 259-269Abstract Full Text PDF PubMed Scopus (16) Google Scholar, 12Buske-Kirschbaum A Hellhammer DH Endocrine and immune responses to stress in chronic inflammatory skin disorders.Ann NY Acad Sci. 2003; 992: 231-240Crossref PubMed Scopus (71) Google Scholar With respect to detrimental reactions to oral antigens, immunogenic material must penetrate the intestinal epithelial barrier to contact and activate immune cells in the lamina propria.13Crowe SE Perdue MH Gastrointestinal food hypersensitivity: basic mechanisms of pathophysiology.Gastroenterology. 1992; 103: 1075-1095PubMed Google Scholar In a sensitized host, immediate hypersensitivity reactions are initiated by antigen cross-linking of specific IgE antibodies bound to the surface of mucosal mast cells located in close proximity beneath the gut epithelium. Released mediators then act on nearby cells to induce both rapid (within minutes) changes in physiology and delayed (within hours to days) effects.13Crowe SE Perdue MH Gastrointestinal food hypersensitivity: basic mechanisms of pathophysiology.Gastroenterology. 1992; 103: 1075-1095PubMed Google Scholar, 14Yang P-C Berin MC Yu LCH Perdue MH Mucosal pathophysiology and inflammatory changes in the late phase of the intestinal allergic reaction in the rat.Am J Pathol. 2001; 158: 681-690Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar In allergic conditions in general, it is not clear how an individual develops sensitivity to a particular antigen. Genetic factors play a role, but persons can develop a hypersensitivity reaction with no family history of atopy.15O'Connell EJ Pediatric allergy: a brief review of risk factors associated with developing allergic disease in childhood.Ann Allergy Asthma Immunol. 2003; 90: 53-58Abstract Full Text PDF PubMed Google Scholar Normally, antigens encountered in the gut lumen induce active suppression of immune/inflammatory responses, known as oral tolerance, rather then a detrimental reaction.16Mayer L Mucosal immunity and gastrointestinal antigen processing.J Pediatr Gastroenterol Nutr. 2000; 30: S4-S12Crossref PubMed Scopus (89) Google Scholar Oral tolerance is not completely understood, but likely involves antigen processing by mucosal cells. Both epithelial and dendritic cells are identified as important cells in this process.16Mayer L Mucosal immunity and gastrointestinal antigen processing.J Pediatr Gastroenterol Nutr. 2000; 30: S4-S12Crossref PubMed Scopus (89) Google Scholar, 17Mowat AM Anatomical basis of tolerance and immunity to intestinal antigens.Nat Rev Immunol. 2003; 3: 331-341Crossref PubMed Scopus (1060) Google Scholar, 18Brandtzaeg P Nature and function of gastrointestinal antigen-presenting cells.Allergy. 2001; 56: S16-S20Crossref PubMed Google Scholar, 19Liu L MacPherson GG Dendritic cells “in vivo”: their role in the initiation of intestinal immune responses.Adv Exp Med Biol. 1995; 371A: 271-274Crossref PubMed Scopus (10) Google Scholar Therefore, the initial events after first encounter with an oral antigen appear to be critical to the outcome of oral tolerance versus sensitization. The gastrointestinal tract, which constitutes one of the largest mucosal sites of exposure of an organism to the outside environment, is lined by a single cell layer of epithelial cells joined together by intercellular tight junctions. This epithelial barrier prevents invasion of microbes and also restricts uptake of macromolecular antigens and other noxious substances that may be present in ingested material. The majority of antigenic proteins are broken down by proteolytic enzymes into nonantigenic fragments before absorption. Some intact antigens are taken up by endocytosis into enterocytes, but are degraded by lysosomal enzymes after fusion of endosomes with lysosomes.20Sanderson IR Walker WA Uptake and transport of macromolecules by the intestine: possible role in clinical disorders (an update).Gastroenterology. 1993; 104: 622-639PubMed Google Scholar Therefore, normally very little antigenic material emerges in the lamina propria. However, under certain conditions, a defect in barrier function allows excessive uptake of intact antigens. Increased permeability has been documented in inflammatory bowel disease21Meddings JB Intestinal permeability in Crohn's disease.Aliment Pharmacol Ther. 1997; 11: S47-S53Crossref PubMed Scopus (79) Google Scholar, 22Soderholm JD Olaison G Lindberg E Hannestad U Vindels A Tysk C Jarnerot G Sjodahl R Different intestinal permeability patterns in relatives and spouses of patients with Crohn's disease: an inherited defect in mucosal defence?.Gut. 1999; 44: 96-100Crossref PubMed Scopus (162) Google Scholar, 23DeMeo MT Mutlu EA Keshavarzian A Tobin MC Intestinal permeation and gastrointestinal disease.J Clin Gastroenterol. 2002; 34: 385-396Crossref PubMed Scopus (234) Google Scholar and at least in a subset of patients with IBS.24Spiller RC Jenkins D Thornley JP Hebden JM Wright T Skinner M Neal KR Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome.Gut. 2000; 47: 804-811Crossref PubMed Scopus (1003) Google Scholar However, at the present time, there is no conclusive information regarding the significance of quantitative or qualitative changes in transepithelial antigen transport in a naive host in terms of its contribution to the development of intestinal hypersensitivity. We have previously reported that psychological stress in rats causes disruption of the epithelial barrier.25Saunders PR Kosecka U McKay DM Perdue MH Acute stressors increase intestinal epithelial permeability and stimulate ion secretion in the rat.Am J Physiol. 1994; 267: G794-G799PubMed Google Scholar, 26Kiliaan AJ Saunders PR Bijlsma PB Berin MC Taminiau JA Groot JA Perdue MH Stress stimulates transepithelial macromolecular uptake in rat jejunum.Am J Physiol. 1998; 275: G1037-G1044PubMed Google Scholar, 27Santos J Saunders PR Hanssen NP Yang PC Yates D Groot JA Perdue MH Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat.Am J Physiol. 1999; 277: G391-G399PubMed Google Scholar, 28Santos J Benjamin M Yang PC Prior T Perdue MH Chronic stress impairs rat growth and jejunal barrier function. Role of mast cells.Am J Physiol. 2000; 278: G847-G854Google Scholar Acute restraint or water avoidance stress (WAS) for 1 hour transiently increases epithelial permeability of both the transcellular and paracellular pathways.26Kiliaan AJ Saunders PR Bijlsma PB Berin MC Taminiau JA Groot JA Perdue MH Stress stimulates transepithelial macromolecular uptake in rat jejunum.Am J Physiol. 1998; 275: G1037-G1044PubMed Google Scholar This effect is mimicked by peripheral (intraperitoneal) administration of the stress hormone, corticotropin-releasing hormone (CRH), and the effects of both CRH and stress are abolished by pretreatment of rats with a general CRH receptor antagonist also administered intraperitoneally.27Santos J Saunders PR Hanssen NP Yang PC Yates D Groot JA Perdue MH Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat.Am J Physiol. 1999; 277: G391-G399PubMed Google Scholar On the other hand, chronic psychological stress results in longer lasting effects: rats exposed to WAS 1 hour per day for 5 to 10 days develop dramatically enhanced macromolecular permeability such that at least 1 week is required for the permeability to normalize.28Santos J Benjamin M Yang PC Prior T Perdue MH Chronic stress impairs rat growth and jejunal barrier function. Role of mast cells.Am J Physiol. 2000; 278: G847-G854Google Scholar, 29Soderholm JD Yang PC Ceponis P Vohra A Riddell R Sherman PM Perdue MH Chronic psychological stress induces mast cell-dependent bacterial adherence to the epithelium and initiates mucosal inflammation in rat intestine.Gastroenterology. 2002; 123: 1099-1108Abstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar Other aspects of abnormal host defense, including adherence of commensal bacterial to epithelial cells and their internalization, have been documented.29Soderholm JD Yang PC Ceponis P Vohra A Riddell R Sherman PM Perdue MH Chronic psychological stress induces mast cell-dependent bacterial adherence to the epithelium and initiates mucosal inflammation in rat intestine.Gastroenterology. 2002; 123: 1099-1108Abstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar This study was designed to test the hypothesis that chronic psychological stress can be a factor involved in inducing sensitization of intestinal tissues to oral antigens. We found that the presence of an antigen load in the intestinal tract during the course of chronic stress increased antigen uptake and resulted in sensitization such that subsequent encounter with antigen stimulated mast cell activation associating with intestinal pathophysiology. Treatment of rats with the CRH antagonist prevented both enhanced transepithelial antigen transport and manifestations of gut hypersensitivity. All procedures were approved by the Animal Care Committee at McMaster University. Male Wistar Kyoto rats (mean body weight 300 g; Charles River Breeding Laboratories, St. Constant, Quebec, Canada), a stress-sensitive strain,25Saunders PR Kosecka U McKay DM Perdue MH Acute stressors increase intestinal epithelial permeability and stimulate ion secretion in the rat.Am J Physiol. 1994; 267: G794-G799PubMed Google Scholar were housed in cages equipped with filter hoods, maintained on a 12:12-hour dark/light cycle, and provided with food and water ad libitum. The rats were exposed to chronic WAS, a psychological stressor that results in a mucosal barrier defect as described.29Soderholm JD Yang PC Ceponis P Vohra A Riddell R Sherman PM Perdue MH Chronic psychological stress induces mast cell-dependent bacterial adherence to the epithelium and initiates mucosal inflammation in rat intestine.Gastroenterology. 2002; 123: 1099-1108Abstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar Briefly, WAS rats were placed on a platform surrounded with water in a container 1 hour per day for 10 consecutive days; sham stress control rats (Con/Ag group) were placed on a similar platform in a container without water. Rats were weighed at the beginning and end of the experiments to confirm the effectiveness of the stress protocol since we previously identified that exposure of rats to chronic WAS inhibits normal weight gain.28Santos J Benjamin M Yang PC Prior T Perdue MH Chronic stress impairs rat growth and jejunal barrier function. Role of mast cells.Am J Physiol. 2000; 278: G847-G854Google Scholar, 29Soderholm JD Yang PC Ceponis P Vohra A Riddell R Sherman PM Perdue MH Chronic psychological stress induces mast cell-dependent bacterial adherence to the epithelium and initiates mucosal inflammation in rat intestine.Gastroenterology. 2002; 123: 1099-1108Abstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar We did not measure corticosterone because preliminary experiments indicated no elevation of this stress hormone at the time of study (10 days after the last stress session). For sensitization, horseradish peroxidase (HRP) (type II; Sigma Chemical Co., St. Louis, MO) was used as the protein antigen. In contrast to earlier studies30Kosecka U Marshall JS Crowe SE Bienenstock J Perdue MH Pertussis toxin stimulates hypersensitivity and enhances nerve-mediated antigen uptake in rat intestine.Am J Physiol. 1994; 267: G745-G753PubMed Google Scholar, 31Berin MC Kiliaan AJ Yang PC Groot JA Taminiau JA Perdue MH Rapid transepithelial antigen transport in rat jejunum: impact of sensitization and the immediate hypersensitivity reaction.Gastroenterology. 1997; 113: 856-864Abstract Full Text PDF PubMed Scopus (151) Google Scholar, 32Crowe SE Sestini P Perdue MH Allergic reactions of rat jejunal mucosa. Ion transport responses to luminal antigen and inflammatory mediators.Gastroenterology. 1990; 99: 74-82Abstract PubMed Google Scholar in which rats were sensitized systemically with a subcutaneous injection of 1 mg of protein [in alum with 50 ng of intraperitoneal pertussis toxin (Sigma) as adjuvants to stimulate IgE production], here we administered HRP by gavage (adjuvants remained the same) immediately after the 1-hour WAS period on day 5 during the course of the 10-day stress protocol. HRP (2 mg in 1 ml of alum) was delivered via an intragastrically positioned cannula. At day 15 after antigen administration (ie, 20 days after beginning the stress procedure), rats were rapidly killed by decapitation. Truncal blood was obtained for serum IgE determinations. Intestinal segments were removed from the jejunum (beginning 5 cm distal to the ligament of Treitz) and pieces were immediately fixed for morphological studies, frozen for mRNA measurements, or prepared for functional studies, as described below. Naïve rats, which were not exposed to stress/sham or antigen, were included as a baseline control group (Con group). In addition, to confirm the role of enhanced gut permeability in the sensitization of rats to oral antigen, a group of WAS rats was treated with the receptor subtype nonspecific CRH antagonist, α-helical CRH9Zar S Kumar D Benson MJ Food hypersensitivity and irritable bowel syndrome.Aliment Pharmacol Ther. 2001; 15: 439-449Crossref PubMed Scopus (107) Google Scholar, 10Marshall GD Agarwal SK Stress, immune regulation, and immunity: applications for asthma.Allergy Asthma Proc. 2000; 21: 241-246Crossref PubMed Scopus (118) Google Scholar, 11Anderzen I Arnetz BB Soderstrom T Soderman E Stress and sensitization in children: a controlled prospective psychophysiological study of children exposed to international relocation.J Psychosom Res. 1997; 43: 259-269Abstract Full Text PDF PubMed Scopus (16) Google Scholar, 12Buske-Kirschbaum A Hellhammer DH Endocrine and immune responses to stress in chronic inflammatory skin disorders.Ann NY Acad Sci. 2003; 992: 231-240Crossref PubMed Scopus (71) Google Scholar, 13Crowe SE Perdue MH Gastrointestinal food hypersensitivity: basic mechanisms of pathophysiology.Gastroenterology. 1992; 103: 1075-1095PubMed Google Scholar, 14Yang P-C Berin MC Yu LCH Perdue MH Mucosal pathophysiology and inflammatory changes in the late phase of the intestinal allergic reaction in the rat.Am J Pathol. 2001; 158: 681-690Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 15O'Connell EJ Pediatric allergy: a brief review of risk factors associated with developing allergic disease in childhood.Ann Allergy Asthma Immunol. 2003; 90: 53-58Abstract Full Text PDF PubMed Google Scholar, 16Mayer L Mucosal immunity and gastrointestinal antigen processing.J Pediatr Gastroenterol Nutr. 2000; 30: S4-S12Crossref PubMed Scopus (89) Google Scholar, 17Mowat AM Anatomical basis of tolerance and immunity to intestinal antigens.Nat Rev Immunol. 2003; 3: 331-341Crossref PubMed Scopus (1060) Google Scholar, 18Brandtzaeg P Nature and function of gastrointestinal antigen-presenting cells.Allergy. 2001; 56: S16-S20Crossref PubMed Google Scholar, 19Liu L MacPherson GG Dendritic cells “in vivo”: their role in the initiation of intestinal immune responses.Adv Exp Med Biol. 1995; 371A: 271-274Crossref PubMed Scopus (10) Google Scholar, 20Sanderson IR Walker WA Uptake and transport of macromolecules by the intestine: possible role in clinical disorders (an update).Gastroenterology. 1993; 104: 622-639PubMed Google Scholar, 21Meddings JB Intestinal permeability in Crohn's disease.Aliment Pharmacol Ther. 1997; 11: S47-S53Crossref PubMed Scopus (79) Google Scholar, 22Soderholm JD Olaison G Lindberg E Hannestad U Vindels A Tysk C Jarnerot G Sjodahl R Different intestinal permeability patterns in relatives and spouses of patients with Crohn's disease: an inherited defect in mucosal defence?.Gut. 1999; 44: 96-100Crossref PubMed Scopus (162) Google Scholar, 23DeMeo MT Mutlu EA Keshavarzian A Tobin MC Intestinal permeation and gastrointestinal disease.J Clin Gastroenterol. 2002; 34: 385-396Crossref PubMed Scopus (234) Google Scholar, 24Spiller RC Jenkins D Thornley JP Hebden JM Wright T Skinner M Neal KR Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome.Gut. 2000; 47: 804-811Crossref PubMed Scopus (1003) Google Scholar, 25Saunders PR Kosecka U McKay DM Perdue MH Acute stressors increase intestinal epithelial permeability and stimulate ion secretion in the rat.Am J Physiol. 1994; 267: G794-G799PubMed Google Scholar, 26Kiliaan AJ Saunders PR Bijlsma PB Berin MC Taminiau JA Groot JA Perdue MH Stress stimulates transepithelial macromolecular uptake in rat jejunum.Am J Physiol. 1998; 275: G1037-G1044PubMed Google Scholar, 27Santos J Saunders PR Hanssen NP Yang PC Yates D Groot JA Perdue MH Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat.Am J Physiol. 1999; 277: G391-G399PubMed Google Scholar, 28Santos J Benjamin M Yang PC Prior T Perdue MH Chronic stress impairs rat growth and jejunal barrier function. Role of mast cells.Am J Physiol. 2000; 278: G847-G854Google Scholar, 29Soderholm JD Yang PC Ceponis P Vohra A Riddell R Sherman PM Perdue MH Chronic psychological stress induces mast cell-dependent bacterial adherence to the epithelium and initiates mucosal inflammation in rat intestine.Gastroenterology. 2002; 123: 1099-1108Abstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar, 30Kosecka U Marshall JS Crowe SE Bienenstock J Perdue MH Pertussis toxin stimulates hypersensitivity and enhances nerve-mediated antigen uptake in rat intestine.Am J Physiol. 1994; 267: G745-G753PubMed Google Scholar, 31Berin MC Kiliaan AJ Yang PC Groot JA Taminiau JA Perdue MH Rapid transepithelial antigen transport in rat jejunum: impact of sensitization and the immediate hypersensitivity reaction.Gastroenterology. 1997; 113: 856-864Abstract Full Text PDF PubMed Scopus (151) Google Scholar, 32Crowe SE Sestini P Perdue MH Allergic reactions of rat jejunal mucosa. Ion transport responses to luminal antigen and inflammatory mediators.Gastroenterology. 1990; 99: 74-82Abstract PubMed Google Scholar, 33Yang P-C Berin MC Yu LCH Conrad DH Perdue MH Enhanced intestinal transepithelial antigen transport in allergic rats is mediated by IgE and CD23 (Fc epsilon RII).J Clin Invest. 2000; 106: 879-886Crossref PubMed Scopus (116) Google Scholar, 34Yu LC Yang PC Berin MC Di Leo V Conrad DH McKay DM Satoskar AR Perdue MH Enhanced transepithelial antigen transport in intestine of sensitized mice is mediated by IgE/CD23 and regulated by interleukin-4.Gastroenterology. 2001; 121: 370-381Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar, 35Cameron HL Yang P-C Perdue MH Glucagon-like peptide-2-enhanced barrier function reduces pathophysiology in a model of food allergy.Am J Physiol. 2000; 284: G905-G912Google Scholar, 36Elenkov IJ Chrousos GP Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease.Trends Endocrinol Metab. 1999; 10: 359-368Abstract Full Text Full Text PDF PubMed Scopus (639) Google Scholar, 37Sampson HA Food allergy.J Allergy Clin Immunol. 2003; 111: S540-S547Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar, 38Bonnefoy JY Aubry JP Gauchat JF Receptors for IgE.Curr Opin Immunol. 1993; 5: 944-949Crossref PubMed Scopus (28) Google Scholar, 39Yu LC Montagnac G Yang PC Conrad DH Benmerah A Perdue MH Intestinal epithelial CD23 mediates enhanced antigen transport in allergy: evidence for novel splice forms.Am J Physiol. 2003; 285: G223-G234Google Scholar, 40Mu HH Sewell WA Enhancement of interleukin-4 production by pertussis toxin.Infect Immun. 1993; 61: 2834-2840PubMed Google Scholar, 41Tu Y Di Leo V Salim S Soderholm JD Marshall J Irvine J Perdue MH CD23/Fc epsilon RII (low affinity IgE receptor) is expressed on human epithelial cells and upregulated by IL-4 and LPS.Gastroenterology. 2001; 120: A188Abstract Full Text PDF Google Scholar (50 μg/kg injected intraperitoneally 30 minutes before each stress session, Sigma), since we had previously inhibited stress-induced mucosal barrier defect by blockade of peripheral CRH receptors.27Santos J Saunders PR Hanssen NP Yang PC Yates D Groot JA Perdue MH Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat.Am J Physiol. 1999; 277: G391-G399PubMed Google Scholar These rats also received HRP by gavage on day 5. The remaining procedures were identical to those described above (αhCRH/WAS/Ag group). One more group of rats were treated only with WAS without exposure to luminal antigen (WAS group). Transepithelial antigen transport and electrophysiological responses to antigen challenge were determined by studying intestinal tissues in Ussing chambers.25Saunders PR Kosecka U McKay DM Perdue MH Acute stressors increase intestinal epithelial permeability and stimulate ion secretion in the rat.Am J Physiol. 1994; 267: G794-G799PubMed Google Scholar, 26Kiliaan AJ Saunders PR Bijlsma PB Berin MC Taminiau JA Groot JA Perdue MH Stress stimulates transepithelial macromolecular uptake in rat jejunum.Am J Physiol. 1998; 275: G1037-G1044PubMed Google Scholar, 27Santos J Saunders PR Hanssen NP Yang PC Yates D Groot JA Perdue MH Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat.Am J Physiol. 1999; 277: G391-G399PubMed Google Scholar, 28Santos J Benjamin M Yang PC Prior T Perdue MH Chronic stress impairs rat growth and jejunal barrier function. Role of mast cells.Am J Physiol. 2000; 278: G847-G854Google Scholar, 29Soderholm JD Yang PC Ceponis P Vohra A Riddell R Sherman PM Perdue MH Chronic psychological stress induces mast cell-dependent bacterial adherence to the epithelium and initiates mucosal inflammation in rat intestine.Gastroenterology. 2002; 123: 1099-1108Abstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar, 30Kosecka U Marshall JS Crowe SE Bienenstock J Perdue MH Pertussis toxin stimulates hypersensitivity and enhances nerve-mediated antigen uptake in rat intestine.Am J Physiol. 1994; 267: G745-G753PubMed Google Scholar, 31Berin MC Kiliaan AJ Yang PC Groot JA Taminiau JA Perdue MH Rapid transepithelial antigen transport in rat jejunum: impact of sensitization and the immediate hypersensitivity reaction.Gastroenterology. 1997; 113: 856-864Abstract Full Text PDF PubMed Scopus (151) Google Scholar, 32Crowe SE Sestini P Perdue MH Allergic reactions of rat jejunal mucosa. Ion transport responses to luminal antigen and inflammatory mediators.Gastroenterology. 1990; 99: 74-82Abstract PubMed Google Scholar From a 10-cm piece of jejunum (10 to 20 cm distal to the ligament of Treitz), the external muscle with adherent mesenteric plexus was carefully removed. For each rat, four adjacent sheets of stripped tissue were mounted in Ussing chambers (WPI Instruments, Narco Scientific, Mississauga, Ontario, Canada), exposing 0.6 cm2 of surface area to Krebs buffer containing 115 mmol/L NaCl, 8 mmol/L KCl, 1.25 mmol/L CaCl2, 1.2 mmol/L MgCl2, 2.0 mmol/L KHPO4, 25 mmol/L NaCO3 (pH 7.35 ± 0.02). The serosal buffer included 10 mmol/L of glucose as an energy source osmotically balanced with 10 mmol/L of mannitol in the luminal/mucosal buffer. A circulating water bath maintained the buffers at 37°C. The electrical current crossing the tissue (a measure of net ion transport) was determined in the voltage-clamp mode (zero volts potential difference) and expressed as short-circuit current (Isc, in μA/cm2). At intervals, the circuit was opened to measure the potential difference, and the tissue conductance (G
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