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Wallon, Conny
Publications (10 of 17) Show all publications
Yakymenko, O., Schoultz, I., Gullberg, E., Ström, M., Almer, S., Wallon, C., . . . Söderholm, J. D. (2018). Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts. Scandinavian Journal of Gastroenterology, 53(6), 677-684
Open this publication in new window or tab >>Infliximab restores colonic barrier to adherent-invasive E. coli in Crohn's disease via effects on epithelial lipid rafts
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2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 6, p. 677-684Article in journal (Refereed) Published
Abstract [en]

Objective: Infliximab is important in the therapeutic arsenal of Crohn’s disease (CD). However, its effect on mucosal barrier function is not fully understood. Adherent-invasive Escherichia coli (AIEC) are important in CD pathophysiology, but the transmucosal uptake routes are partly unknown. We investigated effects of infliximab on uptake of colon-specific AIEC HM427 across CD colonic mucosa.

Materials and methods: Endoscopic biopsies from non-inflamed colon of seven patients with CD, before and after two infliximab infusions, and eight non-inflammation controls, were mounted in Ussing chambers. Paracellular permeability (51Cr-EDTA) and transmucosal passage of GFP-expressing HM427 were studied. Mechanisms of HM427 transepithelial transport were investigated in Caco-2 monolayers treated with TNF, in the presence of infliximab and/or endocytosis inhibitors.

Results: Before infliximab treatment, colonic passage of HM427 [CD: 2475 CFU (450–3000); controls 1163(225–1950)] and 51Cr-EDTA permeability were increased in CD (p < .05), but were restored to control levels by infliximab (CD: 150 (18.8–1069)). In TNF-exposed Caco-2 monolayers HM427 transport and lipid rafts/HM427 co-localization was decreased by infliximab. The lipid raft inhibitor methyl-β-cyclodextrin decreased HM427 transport.

Conclusion: Infliximab restored the colonic barrier to AIEC in CD; an effect partially mediated by blocking lipid rafts in epithelial cells. This ability likely contributes to infliximab’s clinical efficacy in colonic CD.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Inflammatory bowel disease, microbiology, large intestine, intestinal barrier function, adherent invasive E. coli
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-147615 (URN)10.1080/00365521.2018.1458146 (DOI)000438146900008 ()29688802 (PubMedID)
Note

Funding agencies: Swedish Research Council-Medicine [VR-MH 2014-02537]; ALF Grants Region Ostergotland

Available from: 2018-04-27 Created: 2018-04-27 Last updated: 2019-04-30Bibliographically approved
Kurt Schultz, J., Yaqub, S., Wallon, C., Blecic, L., Mjorud Forsmo, H., Folkesson, J., . . . Oresland, T. (2015). Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis The SCANDIV Randomized Clinical Trial. Journal of the American Medical Association (JAMA), 314(13), 1364-1375
Open this publication in new window or tab >>Laparoscopic Lavage vs Primary Resection for Acute Perforated Diverticulitis The SCANDIV Randomized Clinical Trial
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2015 (English)In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 314, no 13, p. 1364-1375Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE Perforated colonic diverticulitis usually requires surgical resection, which is associated with significant morbidity. Cohort studies have suggested that laparoscopic lavage may treat perforated diverticulitis with less morbidity than resection procedures. OBJECTIVE To compare the outcomes from laparoscopic lavage with those for colon resection for perforated diverticulitis. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized clinical superiority trial recruiting participants from 21 centers in Sweden and Norway from February 2010 to June 2014. The last patient follow-up was in December 2014 and final review and verification of the medical records was assessed in March 2015. Patients with suspected perforated diverticulitis, a clinical indication for emergency surgery, and free air on an abdominal computed tomography scan were eligible. Of 509 patients screened, 415 were eligible and 199 were enrolled. INTERVENTIONS Patients were assigned to undergo laparoscopic peritoneal lavage (n = 101) or colon resection (n = 98) based on a computer-generated, center-stratified block randomization. All patients with fecal peritonitis (15 patients in the laparoscopic peritoneal lavage group vs 13 in the colon resection group) underwent colon resection. Patients with a pathology requiring treatment beyond that necessary for perforated diverticulitis (12 in the laparoscopic lavage group vs 13 in the colon resection group) were also excluded from the protocol operations and treated as required for the pathology encountered. MAIN OUTCOMES AND MEASURES The primary outcome was severe postoperative complications (Clavien-Dindo score greater thanIlla) within 90 days. Secondary outcomes included other postoperative complications, reoperations, length of operating time, length of postoperative hospital stay, and quality of life. RESULTS The primary outcome was observed in 31 of 101 patients (30.7%) in the laparoscopic lavage group and 25 of 96 patients (26.0%) in the colon resection group (difference, 4.7% [95% CI, -7.9% to 17.0%]; P = .53). Mortality at 90 days did not significantly differ between the laparoscopic lavage group (14 patients [13.9%]) and the colon resection group (11 patients [11.5%]; difference, 2.4% [95% CI, -7.2% to 11.9%]; P = .67). The reoperation rate was significantly higher in the laparoscopic lavage group (15 of 74 patients [20.3%]) than in the colon resection group (4 of 70 patients [5.7%]; difference, 14.6% [95% CI, 3.5% to 25.6%]; P = .01) for patients who did not have fecal peritonitis. The length of operating time was significantly shorter in the laparoscopic lavage group; whereas, length of postoperative hospital stay and quality of life did not differ significantly between groups. Four sigmoid carcinomas were missed with laparoscopic lavage. CONCLUSIONS AND RELEVANCE Among patients with likely perforated diverticulitis and undergoing emergency surgery, the use of laparoscopic lavage vs primary resection did not reduce severe postoperative complications and led to worse outcomes in secondary end points. These findings do not support laparoscopic lavage for treatment of perforated diverticulitis.

Place, publisher, year, edition, pages
AMER MEDICAL ASSOC, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-122777 (URN)10.1001/jama.2015.12076 (DOI)000362644700014 ()26441181 (PubMedID)
Note

Funding Agencies|South-Eastern Norway Regional Health Authority [PNR 2719011]; Akershus University Hospital [PNR 2619041, 2629038, 2649054]

Available from: 2015-11-23 Created: 2015-11-23 Last updated: 2017-12-01
Persborn, M., Gerritsen, J., Wallon, C., Carlsson, A., Akkermans, L. M. & Söderholm, J. D. (2013). The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis. Alimentary Pharmacology and Therapeutics, 38(7), 772-783
Open this publication in new window or tab >>The effects of probiotics on barrier function and mucosal pouch microbiota during maintenance treatment for severe pouchitis in patients with ulcerative colitis
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2013 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 38, no 7, p. 772-783Article in journal (Refereed) Published
Abstract [en]

Background less thanbrgreater than less thanbrgreater thanA total of 10-15% of patients with an ileoanal pouch develop severe pouchitis necessitating long-term use of antibiotics or pouch excision. Probiotics reduce the risk of recurrence of pouchitis, but mechanisms behind these effects are not fully understood. less thanbrgreater than less thanbrgreater thanAim less thanbrgreater than less thanbrgreater thanTo examine mucosal barrier function in pouchitis, before and after probiotic supplementation and to assess composition of mucosal pouch microbiota. less thanbrgreater than less thanbrgreater thanMethods less thanbrgreater than less thanbrgreater thanSixteen patients with severe pouchitis underwent endoscopy with biopsies of the pouch on three occasions: during active pouchitis; clinical remission by 4 weeks of antibiotics; after 8 weeks of subsequent probiotic supplementation (Ecologic 825, Winclove, Amsterdam, the Netherlands). Thirteen individuals with a healthy ileoanal pouch were sampled once as controls. Ussing chambers were used to assess transmucosal passage of Escherichia coli K12, permeability to horseradish peroxidase (HRP) and Cr-51-EDTA. Composition and diversity of the microbiota was analysed using Human Intestinal Tract Chip. less thanbrgreater than less thanbrgreater thanResults less thanbrgreater than less thanbrgreater thanPouchitis Disease Activity Index (PDAI) was significantly improved after antibiotic and probiotic supplementation. Escherichia coli K12 passage during active pouchitis [3.7 (3.4-8.5); median (IQR)] was significantly higher than in controls [1.7 (1.0-2.4); P andlt; 0.01], did not change after antibiotic treatment [5.0 (3.3-7.1); P = ns], but was significantly reduced after subsequent probiotic supplementation [2.2 (1.7-3.3); P andlt; 0.05]. No significant effects of antibiotics or probiotics were observed on composition of mucosal pouch microbiota; however, E. coli passage correlated with bacterial diversity (r = -0.40; P = 0.018). Microbial groups belonging to Bacteroidetes and Clostridium clusters IX, XI and XIVa were associated with healthy pouches. less thanbrgreater than less thanbrgreater thanConclusions less thanbrgreater than less thanbrgreater thanProbiotics restored the mucosal barrier to E. coli and HRP in patients with pouchitis, a feasible factor in prevention of recurrence during maintenance treatment. Restored barrier function did not translate into significant changes in mucosal microbiota composition, but bacterial diversity correlated with barrier function.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-98215 (URN)10.1111/apt.12451 (DOI)000323843900011 ()
Note

Funding Agencies|Swedish Research Council - Medicine||Research Council of South-East Sweden (FORSS)||County Council of Ostergotland||County Council of Jonkoping||SenterNovem (Agentschap NL), an agency of the Dutch Ministry of Economic Affairs|FND-07013|

Available from: 2013-10-03 Created: 2013-10-03 Last updated: 2017-12-06
Al-Ayoubi, F., Eriksson, H., Myrelid, P., Wallon, C. & Andersson, P. (2012). Uneven distribution of emergency operations and lack of trauma: a call for reorganization of acute surgical care?. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 20
Open this publication in new window or tab >>Uneven distribution of emergency operations and lack of trauma: a call for reorganization of acute surgical care?
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2012 (English)In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 20Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Subspecialisation within general surgery has today reached further than ever. However, on-call time, an unchanged need for broad surgical skills are required to meet the demands of acute surgical disease and trauma. The introduction of a new subspecialty in North America that deals solely with acute care surgery and trauma is an attempt to offer properly trained surgeons also during on-call time. To find out whether such a subspecialty could be helpful in Sweden we analyzed our workload for emergency surgery and trauma. METHODS: Linkoping University Hospital serves a population of 257 000. Data from 2010 for all patients, diagnoses, times and types of operations, surgeons involved, duration of stay, types of injury and deaths regarding emergency procedures were extracted from a prospectively-collected database and analyzed. RESULTS: There were 2362 admissions, 1559 emergency interventions; 835 were mainly abdominal operations, and 724 diagnostic or therapeutic endoscopies. Of the 1559 emergency interventions, 641 (41.1%) were made outside office hours, and of 453 minor or intermediate procedures (including appendicectomy, cholecystectomy, or proctological procedures) 276 (60.9%) were done during the evenings or at night. Two hundred and fifty-four patients were admitted with trauma and 29 (11.4%) required operation, of whom general surgeons operated on eight (3.1%). Thirteen consultants and 11 senior registrars were involved in 138 bowel resections and 164 cholecystectomies chosen as index operations for standard emergency surgery. The median (range) number of such operations done by each consultant was 6 (3--17) and 6 (1--22). Corresponding figures for senior registrars were 7 (0--11) and 8 (1--39). CONCLUSION: There was an uneven distribution of exposure to acute surgical problems and trauma among general surgeons. Some were exposed to only a few standard emergency interventions and most surgeons did not operate on a single patient with trauma. Further centralization of trauma care, long-term positions at units for emergency surgery and trauma, and subspecialisation in the fields of emergency surgery and trauma, might be options to solve problems of low volumes.

Place, publisher, year, edition, pages
BioMed Central, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-87677 (URN)10.1186/1757-7241-20-66 (DOI)22985447 (PubMedID)
Available from: 2013-01-22 Created: 2013-01-21 Last updated: 2017-12-06
Wallon, C., Persborn, M., Jönsson, M., Wang, A., Phan, V., Lampinen, M., . . . Söderholm, J. D. (2011). Eosinophils Express Muscarinic Receptors and Corticotropin-Releasing Factor to Disrupt the Mucosal Barrier in Ulcerative Colitis. Gastroenterology, 140(5), 1597-1607
Open this publication in new window or tab >>Eosinophils Express Muscarinic Receptors and Corticotropin-Releasing Factor to Disrupt the Mucosal Barrier in Ulcerative Colitis
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2011 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 140, no 5, p. 1597-1607Article in journal (Refereed) Published
Abstract [en]

BACKGROUND andamp; AIMS: Altered intestinal barrier function has been implicated in the pathophysiology of ulcerative colitis (UC) in genetic, functional, and epidemiological studies. Mast cells and corticotropinreleasing factor (CRF) regulate the mucosal barrier in human colon. Because eosinophils are often increased in colon tissues of patients with UC, we assessed interactions among mast cells, CRF, and eosinophils in the mucosal barrier of these patients. METHODS: Transmucosal fluxes of protein antigens (horseradish peroxidase) and paracellular markers (51Cr-EDTA, fluorescein isothiocyanate-dextran 4000) were studied in noninflamed, colonic mucosal biopsy samples collected from 26 patients with UC and 53 healthy volunteers (controls); samples were mounted in Ussing chambers. We also performed fluorescence and electron microscopy of human tissue samples, assessed isolated eosinophils, and performed mechanistic studies using in vitro cocultured eosinophils (15HL-60), mast cells (HMC-1), and a colonic epithelial cell line (T84). RESULTS: Colon tissues from patients with UC had significant increases in permeability to protein antigens compared with controls. Permeability was blocked by atropine (a muscarinic receptor antagonist), alpha-helical CRF(9-41) (a CRF receptor antagonist), and lodoxamide (a mast-cell stabilizer). Eosinophils were increased in number in UC tissues (compared with controls), expressed the most M2 and M3 muscarinic receptors of any mucosal cell type, and had immunoreactivity to CRF. In coculture studies, carbachol activation of eosinophils caused production of CRF and activation of mast cells, which increased permeability of T84 epithelial cells to macromolecules. CONCLUSIONS: We identified a neuroimmune intercellular circuit (from cholinergic nerves, via eosinophils to mast cells) that mediates colonic mucosal barrier dysfunction in patients with UC. This circuit might exacerbate mucosal inflammation.

Place, publisher, year, edition, pages
Elsevier Science B.V. Amsterdam, 2011
Keywords
Intestinal Permeability, Inflammatory Bowel Disease, Immune Response, Stress
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68223 (URN)10.1053/j.gastro.2011.01.042 (DOI)000290028200040 ()
Available from: 2011-05-13 Created: 2011-05-13 Last updated: 2017-12-11
Wallon, C., Juhlin, C., Melander, H. & Sjödahl, R. (2010). Oplanerade återinläggningar på kirurgisk klinik. Läkartidningen, 107(23), 1548-1551
Open this publication in new window or tab >>Oplanerade återinläggningar på kirurgisk klinik
2010 (English)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 23, p. 1548-1551Article in journal (Refereed) Published
Abstract [en]

[No abstract available]

Place, publisher, year, edition, pages
Lakartidningen, 2010
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-59110 (URN)
Available from: 2010-09-20 Created: 2010-09-09 Last updated: 2017-12-12
Wallon, C. & Söderholm, J. D. (2009). Corticotropin-Releasing Hormone and Mast Cells in the Regulation of Mucosal Barrier Function in the Human Colon. MOLECULAR STRUCTURE AND FUNCTION OF THE TIGHT JUNCTION: FROM BASIC MECHANISMS TO CLINICAL MANIFESTATIONS, 1165, 206-210
Open this publication in new window or tab >>Corticotropin-Releasing Hormone and Mast Cells in the Regulation of Mucosal Barrier Function in the Human Colon
2009 (English)In: MOLECULAR STRUCTURE AND FUNCTION OF THE TIGHT JUNCTION: FROM BASIC MECHANISMS TO CLINICAL MANIFESTATIONS, ISSN 0077-8923, Vol. 1165, p. 206-210Article in journal (Refereed) Published
Abstract [en]

Corticotropin-releasing hormone (CRH) is an important neuro-endocrine mediator of the stress response. Local effects of CRH in the intestinal mucosa have become evident in recent years. We showed that CRH activates CRH receptor subtypes R1 and R2 on subepithelial mast cells, thereby inducing increased transcellular uptake of protein antigens in human colonic biopsies in Ussing chambers. Ongoing studies also implicate local cholinergic signaling in regulation of macromolecular permeability in the human colon. Since increased uptake of antigenic molecules is associated with mucosal inflammation, our findings may have implications for understanding stress-related intestinal disorders.

Keywords
CRH receptor; Ussing chamber; stress; electron microscopy; transcytosis; intestinal mucosa
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20216 (URN)10.1111/j.1749-6632.2009.04030.x (DOI)
Available from: 2009-09-02 Created: 2009-08-31 Last updated: 2009-09-02
Wallon, C., Yang, P., Keita, Å., Ericson, A.-C., McKay, D. M., Sherman, P. M., . . . Söderholm, J. D. (2008). Corticotropin releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro. Gut, 57(1), 50-58
Open this publication in new window or tab >>Corticotropin releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro
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2008 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, no 1, p. 50-58Article in journal (Refereed) Published
Abstract [en]

Objective: Persistent stress and life events affect the course of ulcerativecolitis and irritable bowel syndrome by largely unknown mechanisms.Corticotropin-releasing hormone (CRH) has been implicated asan important mediator of stress-induced abnormalities in intestinalmucosal function in animal models, but to date no studies inhuman colon have been reported. The aim was to examine the effectsof CRH on mucosal barrier function in the human colon and toelucidate the mechanisms involved in CRH-induced hyper-permeability.

Design: Biopsies from 39 volunteers were assessed for macromolecularpermeability (horseradish peroxidise (HRP), 51Cr-EDTA), andelectrophysiology after CRH challenge in Ussing chambers. Thebiopsies were examined by electron and confocal microscopy forHRP and CRH receptor localisation, respectively. Moreover, CRHreceptor mRNA and protein expression were examined in the humanmast cell line, HMC-1.

Results: Mucosal permeability to HRP was increased by CRH (2.8±0.5pmol/cm2/h) compared to vehicle exposure (1.5±0.4 pmol/cm2/h),p = 0.032, whereas permeability to 51Cr-EDTA and transmucosalelectrical resistance were unchanged. The increased permeabilityto HRP was abolished by -helical CRH (9-41) (1.3±0.6pmol/cm2/h) and the mast cell stabiliser, lodoxamide (1.6±0.6pmol/cm2/h). Electron microscopy showed transcellular passageof HRP through colonocytes. CRH receptor subtypes R1 and R2were detected in the HMC-1 cell line and in lamina propria mastcells in human colon.

Conclusions: Our results suggest that CRH mediates transcellular uptake ofHRP in human colonic mucosa via CRH receptor subtypes R1 andR2 on subepithelial mast cells. CRH-induced macromolecular uptakein human colon mucosa may have implications for stress-relatedintestinal disorders.

Place, publisher, year, edition, pages
London UK: BMJ Group, 2008
Keywords
CRH receptor subtypes, barrier function, electron microscopy, human mast cell line, intestinal mucosa
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-13153 (URN)10.1136/gut.2006.117549 (DOI)000251778400013 ()
Available from: 2008-04-07 Created: 2008-04-07 Last updated: 2017-12-13Bibliographically approved
Wallon, C. (2007). Neuro-immune regulation of macromolecular permeability in the normal human colon and in ulcerative colitis. (Doctoral dissertation). Institutionen för klinisk och experimentell medicin
Open this publication in new window or tab >>Neuro-immune regulation of macromolecular permeability in the normal human colon and in ulcerative colitis
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aim: Persistent stress and life events affect the course of ulcerative colitis (UC) by largely unknown mechanisms. Regulation of epithelial permeability to antigens is crucial for the balance between inflammation and immuno-surveillance, and increased intestinal permeability has been shown in patients with ulcerative colitis. Corticotropin releasing hormone (CRH) has been implicated as an important mediator of stress-induced abnormalities in intestinal mucosal function in animal models. Further cholinergic signalling during stress

has been reported to increase bowel ion secretion in humans and uptake of HRP in rodents via activation of mast cells.

The overall aim of this thesis was to examine the role of CRH-mediated and cholinergic signalling, and their interaction with mast cells and eosinophils, in the regulation of the mucosal barrier function in the normal human colon and in UC. In vivo studies or the use of surgical specimens for such studies have major shortcomings. Therefore a method with endoscopic biopsies in Ussing chambers was established for studies of protein antigen uptake and electrophysiology in human colonic biopsies, and used in subsequent investigations.

Materials and methods: In the four studies a total of 91 healthy volunteers, 3 patients with rectal cancer, and 15 UC patients were included. Biopsies from the sigmoid colon were assessed for macromolecular permeability (Horseradish peroxidase (HRP), and 51Cr-EDTA), and electrophysiology during challenge with sodium caprate (C10), CRH or carbachol. Experiments were repeated with CRH receptor antagonists, carbachol receptor antagonists, mast cell stabilizers and nerve conductance blockers in Ussing chambers. The biopsies were examined by electron and light microscopy for endocytosis of HRP, morphological changes and receptor expression. Moreover, the human mast cell line, HMC-1; was used in studying expression of CRH receptors on mast cells.

Results: Endoscopic biopsies of human colon were viable in Ussing chambers, and the technique was shown to be a reliable tool for studies of mucosal permeability to HRP. CRH stimulates transcellular uptake of HRP in human colon via CRH receptor subtypes R1 and R2 on subepithelial mast cells. Further, carbachol acts on muscarinic receptors, located on subepithelial eosinophils. Activated muscarinic M2 and M3 receptors on increased numbers of CRHproducing eosinophils in UC, lead to activation of mast cells and increased macromolecular uptake across the colonic mucosa. This signalling cascade is previously unrecognized, and may be involved in the inflammatory process in UC.

Conclusions: In conclusion, we have demonstrated a chain of events leading to increased permeability to the protein antigen HRP in biopsies from healthy volunteers and patients with UC. The important steps begin with a cholinergic signal to muscarinic receptors on the CRH containing eosinophils. The next step includes activation of CRH receptors on mast cells leading to degranulation and increased macromolecular uptake across the epithelium. This explanatory model will have implications for understanding of the pathogenesis of UC and future treatment of the disease.

Place, publisher, year, edition, pages
Institutionen för klinisk och experimentell medicin, 2007. p. 75
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1022
Keywords
Colitis, ulcerative, colon, sigmoid, cytology, immunohistochemistry
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-11496 (URN)978-91-85895-68-7 (ISBN)
Public defence
2007-12-14, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2008-04-07 Created: 2008-04-07 Last updated: 2009-08-22
Keita, Å. V., Gullberg, E., Ericson, A.-C., Salim, S. Y., Wallon, C., Kald, A., . . . Söderholm, J. D. (2006). Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum. Laboratory investigation, 86(5), 504-516
Open this publication in new window or tab >>Characterization of antigen and bacterial transport in the follicle-associated epithelium of human ileum
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2006 (English)In: Laboratory investigation, ISSN 0023-6837, Vol. 86, no 5, p. 504-516Article in journal (Refereed) Published
Abstract [en]

The follicle-associated epithelium (FAE), covering Peyer's patches, provides a route of entry for antigens and microorganisms. Animal studies showed enhanced antigen and bacterial uptake in FAE, but no study on barrier function of human FAE has been reported. Our aim was to characterize the normal barrier properties of human FAE. Specimens of normal ileum were taken from 30 patients with noninflammatory colonic disease. Villus epithelium (VE) and FAE were identified and mounted in Ussing chambers. Permeability to 51Cr-EDTA, transmucosal flux of the protein antigen, horseradish peroxidase (HRP), and transport of fluorescent Escherichia coli (chemically killed K-12 and live HB101) were measured. Uptake mechanisms were studied by confocal- and transmission electron microscopy, and by using pharmacological inhibitors in an in vitro coculture model of FAE and in human ileal FAE. HRP flux was substantially higher in FAE than in VE, and was reduced by an amiloride analog. Electron microscopy showed HRP-containing endosomes. Transport of E. coli K-12 and HB101 was also augmented in FAE and was confirmed by confocal microscopy. In vitro coculture experiments and electron microscopy revealed actin-dependent, mainly transcellular, uptake of E. coli K-12 into FAE. 51Cr-EDTA permeability was equal in FAE and VE. Augmented HRP flux and bacterial uptake but similar paracellular permeability, suggest functional variations of transcellular transport in the FAE. We show for the first time that FAE of human ileum is functionally distinct from regular VE, rendering the FAE more prone to bacterial–epithelial cell interactions and delivery of antigens to the mucosal immune system.

Keywords
E. coli, horseradish peroxidase, M cell, permeability, Peyer's patches
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14563 (URN)10.1038/labinvest.3700397 (DOI)
Available from: 2007-07-03 Created: 2007-07-03
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