UBC Faculty Research and Publications

Adhesion molecules in experimental peanut allergy Bennett, Jami; Maltby, Steven; Frohwerk, Erin; Jian, Kay; Merkens, Helen; Tunis, Mathew; McNagny, Kelly Nov 26, 2010

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POSTER PRESENTATION Open AccessAdhesion molecules in experimental peanutallergyJami Bennett1, Steven Maltby1, Erin Frohwerk1, Kay Jian1, Helen Merkens1, Mathew Tunis2, Kelly McNagny1*From AllerGen NCE Inc.’s Fifth Annual Research Conference: Innovation from Cell to SocietyQuébec City, QC, Canada. 7-9 February 2010Objective/purposeAdhesion molecules are critical for appropriate localiza-tion of leukocytes and induction of adaptive immuneresponses throughout the body. Our aim is to betterunderstand the role of cell trafficking and adhesionmolecules in an experimental model of peanut allergy.MethodsPeanut allergy was induced in mice on the C57Bl/6background (IAb) with 4 weekly oral gavage feedings ofpeanut protein and cholera toxin. After a two-week restperiod, sensitized animals were challenged by intraperi-toneal injection with crude peanut extract (CPE) andmonitored for anaphylaxis. Clinical indicators of peanutallergy include decreased body temperature, scratching,swollen eyes, decreased movement and responsiveness,and moribund condition. We evaluated plasma hista-mine, total IgE, peanut-specific IgE, and peritoneal albu-min levels as in vivo indicators of mast celldegranulation and vascular permeability.Targeted genes and phenotypesCD34-/-Normally a surface marker of hematopoietic stem cells,mast cells, eosinophils and DCs, required for efficientcell migration. Mice exhibit attenuation of most mucosalinflammatory disease models.CD103-/-Alpha-chain of integrin expressed by mucosal DCs andT cells which facilitates binding to mucosal epithelialcells; Mice exhibit exacerbated Th2 inflammatoryresponses.IL7-Ra-/-Required for T cell homing and efficient T and B celldevelopment. Mice exhibit impaired adaptive immuneresponses.L-Selectin-/-Adhesion molecule required for appropriate localizationof naïve lymphocytes to primary lymphoid tissue. Miceexhibit impaired primary adaptive immune responses.PSGL-1-/- and E-Selectin-/-Adhesion molecules required for efficient homing ofinflammatory cells to the sites of inflammation. Miceexhibit attenuated inflammatory responses.FindingsCD34, CD103, PSGL-1, E-Selectin, and probably P-Selectin are likely dispensible for induction of experi-mental peanut allergies since deficient animals are fullysusceptible to peanut induced anaphylaxis. This likelyreflects the fact that, although each of these mice exhibita delay in the induction of inflammatory disease, noneexhibit a complete block in inflammatory homing. Sinceour evaluation of acute allergic reactions occurs afterseveral priming steps it is likely that these mice exhibitsufficient inflammatory homing to render them suscepti-ble to an acute challenge. In stark contrast, adhesionmolecules required for the appropriate localization oflymphocytes prior to sensitization (L-Selectin) and thoserequired for efficient formation of adaptive immunecells (IL7-Ra) are required for induction of peanutinduced anaphylaxis since mice lacking these moleculesexhibited a strong protection from anaphylaxis.DeliverablesOur data suggest that, with the exception of L-Selectin,most of the molecules known to play a role in leukocyte* Correspondence: Kelly@brc.ubc.ca1Biomedical Research Centre, University of British Columbia, Vancouver,British Columbia, CanadaFull list of author information is available at the end of the articleBennett et al. Allergy, Asthma & Clinical Immunology 2010, 6(Suppl 3):P10http://www.aacijournal.com/content/6/S3/P10 ALLERGY, ASTHMA & CLINICAL IMMUNOLOGY© 2010 Bennett et al; licensee BioMed Central Ltd.homing do not play a major role in acute allergen-induced anaphylaxis and would, therefore, be poor tar-gets for therapy. Future studies will focus on how L-Selectin inactivation leads to amelioration of peanutallergies. We will test relevant methods of interferingwith this site-specific function and attempt to blockantigen transit/priming without breaking oral toleranceto other antigens routinely encountered in the gut.RelevanceFood allergy and peanut allergy in particular, is a majorhealth challenge for many young people in Canada.Understanding the role of immune cell function andlocalization is critical to our ability to modulate mucosalinflammation and disease. Our findings will informfuture efforts to generate therapies for food allergicpatients and identify or eliminate potential therapeutictargets for food allergy, ultimately enhancing the thera-peutic options and quality of life for affected patients.These data will be published in peer-reviewed journals,presented in abstracts and seminars, and reported aspart of the CanGoFAR project summary to deliver thefindings to the community and relevant policy makers.AcknowledgementsResearch funded by CanGoFAR/Hematopoietic Stem Cell Markers inDiagnosis & Prediction of Allergic Inflammation & Disease; PostdoctoralFellowship, Multiple Sclerosis Society of Canada (JLB), PostgraduateScholarship-Doctoral, Natural Sciences and EngineeringResearch Council(EJF); Strategic Training Program in Transfusion Science, CIHR/HSFC throughCBR (SM), Research Scholar, Michael Smith Foundation for Health Research(KMM), and operating funds from CIHR (Canadian Institutes of HealthResearch)Author details1Biomedical Research Centre, University of British Columbia, Vancouver,British Columbia, Canada. 2Department of Microbiology & Immunology,Dalhousie University, Halifax, Nova Scotia, Canada.Published: 26 November 2010doi:10.1186/1710-1492-6-S3-P10Cite this article as: Bennett et al.: Adhesion molecules in experimentalpeanut allergy. Allergy, Asthma & Clinical Immunology 2010 6(Suppl 3):P10.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitBennett et al. Allergy, Asthma & Clinical Immunology 2010, 6(Suppl 3):P10http://www.aacijournal.com/content/6/S3/P10Page 2 of 2

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