Blood eosinophil numbers may be elevated in allergy, inflammatory bowel disease and eosinophilic esophagitis. The aim of this study was to examine whether circulating eosinophils display distinct phenotypes in these disorders and if different patterns of eosinophilic chemoattractants exist. Blood eosinophils from patients with symptomatic eosinophilic esophagitis (EoE; n = 12), ulcerative colitis (n = 8), airway allergy (n = 10) and healthy controls (n = 10) were enumerated and their surface markers analyzed by flow cytometry. Plasma levels of pro-eosinophilic cytokines were quantified in parallel. Data were processed by multivariate pattern recognition methods to reveal disease-specific patterns of eosinophil phenotypes and cytokines. EoE patients had higher numbers of eosinophils with enhanced expression of CD23, CD54, CRTH2 and CD11c and diminished CCR3 and CD44 expression. Plasma CCL5 was also increased in EoE. Although allergic patients had increased interleukin (IL)-2, IL-3, IL-5 and granulocyte macrophage colony-stimulating factor plasma concentrations, their blood eosinophil phenotypes were indistinguishable from those of healthy controls. Decreased eosinophilic expression of CD11b, CD18, CD44 and CCR3, but no distinctive pattern of eosinophil chemoattractants, characterized ulcerative colitis. We propose that eosinophils acquire varying functional properties as a consequence of distinct patterns of activation signals released from the inflamed tissues in different diseases.
© 2011 S. Karger AG, Basel
- Inflammatory bowel disease
- Eosinophilic esophagitis
- Flow cytometry
- Bischoff SC, Wedemeyer J, Herrmann A, Meier PN, Trautwein C, Cetin Y, Maschek H, Stolte M, Gebel M, Manns MP: Quantitative assessment of intestinal eosinophils and mast cells in inflammatory bowel disease. Histopathology 1996;28:1–13.
- Carvalho AT, Elia CC, de Souza HS, Elias PR, Pontes EL, Lukashok HP, de Freitas FC, Lapa e Silva JR: Immunohistochemical study of intestinal eosinophils in inflammatory bowel disease. J Clin Gastroenterol 2003;36:120–125.
- Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME: Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 2007;133:1342–1363.
- Straumann A, Simon HU: Eosinophilic esophagitis: escalating epidemiology? J Allergy Clin Immunol 2005;115:418–419.
- Spergel JM: Eosinophilic esophagitis in adults and children: evidence for a food allergy component in many patients. Curr Opin Allergy Clin Immunol 2007;7:274–278.
- Gauvreau GM, Ellis AK, Denburg JA: Haemopoietic processes in allergic disease: eosinophil/basophil development. Clin Exp Allergy 2009;39:1297–1306.
- Kato M, Kephart GM, Talley NJ, Wagner JM, Sarr MG, Bonno M, McGovern TW, Gleich GJ: Eosinophil infiltration and degranulation in normal human tissue. Anat Rec 1998;252:418–425.
- Lampinen M, Carlson M, Hakansson LD, Venge P: Cytokine-regulated accumulation of eosinophils in inflammatory disease. Allergy 2004;59:793–805.
- Plotz SG, Traidl-Hoffmann C, Feussner I, Kasche A, Feser A, Ring J, Jakob T, Behrendt H: Chemotaxis and activation of human peripheral blood eosinophils induced by pollen-associated lipid mediators. J Allergy Clin Immunol 2004;113:1152–1160.
- Redvall E, Bengtsson U, Wenneras C: Responsiveness of eosinophils to aeroallergens may be independent of atopic status. Scand J Immunol 2008;67:377–384.
- Svensson L, Redvall E, Bjorn C, Karlsson J, Bergin AM, Rabiet MJ, Dahlgren C, Wenneras C: House dust mite allergen activates human eosinophils via formyl peptide receptor and formyl peptide receptor-like 1. Eur J Immunol 2007;37:1966–1977.
- Svensson L, Wenneras C: Human eosinophils selectively recognize and become activated by bacteria belonging to different taxonomic groups. Microbes Infect 2005;7:720–728.
- Stenfeldt AL, Wenneras C: Danger signals derived from stressed and necrotic epithelial cells activate human eosinophils. Immunology 2004;112:605–614.
- Nair P, Pizzichini MM, Kjarsgaard M, Inman MD, Efthimiadis A, Pizzichini E, Hargreave FE, O’Byrne PM: Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985–993.
- Shichijo K, Makiyama K, Wen CY, Matsuu M, Nakayama T, Nakashima M, Ihara M, Sekine I: Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats. World J Gastroenterol 2005;11:4505–4510.
- Heatley RV, James PD: Eosinophils in the rectal mucosa. A simple method of predicting the outcome of ulcerative proctocolitis? Gut 1979;20:787–791.
- Flood-Page P, Menzies-Gow A, Phipps S, Ying S, Wangoo A, Ludwig MS, Barnes N, Robinson D, Kay AB: Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest 2003;112:1029–1036.
- Jacobsen EA, Taranova AG, Lee NA, Lee JJ: Eosinophils: singularly destructive effector cells or purveyors of immunoregulation? J Allergy Clin Immunol 2007;119:1313–1320.
- Svensson L, Dahlgren C, Wenneras C: The chemoattractant Trp-Lys-Tyr-Met-Val-D-Met activates eosinophils through the formyl peptide receptor and one of its homologues, formyl peptide receptor-like 1. J Leukoc Biol 2002;72:810–818.
- Roederer M: Compensation in flow cytometry; in Robinson JP: Current Protocols in Cytometry. New York, John Wiley and Sons, 2002, suppl 22, pp 1.14.11–11.14.20.
- Eriksson L, Antti H, Gottfries J, Holmes E, Johansson E, Lindgren F, Long I, Lundstedt T, Trygg J, Wold S: Using chemometrics for navigating in the large data sets of genomics, proteomics, and metabonomics (gpm). Anal Bioanal Chem 2004;380:419–429.
- Heinemann A, Schuligoi R, Sabroe I, Hartnell A, Peskar BA: Delta 12-prostaglandin J2, a plasma metabolite of prostaglandin D2, causes eosinophil mobilization from the bone marrow and primes eosinophils for chemotaxis. J Immunol 2003;170:4752–4758.
- Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, Beglinger C, Smith DA, Patel J, Byrne M, Simon HU: Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 2010;59:21–30.
- Alam R, Stafford S, Forsythe P, Harrison R, Faubion D, Lett-Brown MA, Grant JA: RANTES is a chemotactic and activating factor for human eosinophils. J Immunol 1993;150:3442–3448.
- Straumann A, Bauer M, Fischer B, Blaser K, Simon HU: Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic inflammatory response. J Allergy Clin Immunol 2001;108:954–961.
- Blanchard C, Wang N, Stringer KF, Mishra A, Fulkerson PC, Abonia JP, Jameson SC, Kirby C, Konikoff MR, Collins MH, Cohen MB, Akers R, Hogan SP, Assa’ad AH, Putnam PE, Aronow BJ, Rothenberg ME: Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest 2006;116:536–547.
- Zimmermann N, Rothenberg ME: Receptor internalization is required for eotaxin-induced responses in human eosinophils. J Allergy Clin Immunol 2003;111:97–105.
- Kim JT, Gleich GJ, Kita H: Roles of CD9 molecules in survival and activation of human eosinophils. J Immunol 1997;159:926–933.
- Abdelilah SG, Bouchaïb L, Morita M, Delphine A, Marika S, André C, Monique C: Molecular characterization of the low-affinity IgE receptor Fc epsilonRII/CD23 expressed by human eosinophils. Int Immunol 1998;10:395–404.
- Vicario M, Blanchard C, Stringer KF, Collins MH, Mingler MK, Ahrens A, Putnam PE, Abonia JP, Santos J, Rothenberg ME: Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis. Gut 2010;59:12–20.
- Bonnefoy JY, Gauchat JF, Life P, Graber P, Aubry JP, Lecoanet-Henchoz S: Regulation of IgE synthesis by CD23/CD21 interaction. Int Arch Allergy Immunol 1995;107:40–42.
- van der Heijden FL, Joost van Neerven RJ, van Katwijk M, Bos JD, Kapsenberg ML: Serum-IgE-facilitated allergen presentation in atopic disease. J Immunol 1993;150:3643–3650.
- Hansel TT, De Vries IJ, Carballido JM, Braun RK, Carballido-Perrig N, Rihs S, Blaser K, Walker C: Induction and function of eosinophil intercellular adhesion molecule-1 and HLA-DR. J Immunol 1992;149:2130–2136.
- Akuthota P, Wang HB, Spencer LA, Weller PF: Immunoregulatory roles of eosinophils: a new look at a familiar cell. Clin Exp Allergy 2008;38:1254–1263.
- Lampinen M, Backman M, Winqvist O, Rorsman F, Ronnblom A, Sangfelt P, Carlson M: Different regulation of eosinophil activity in Crohn’s disease compared with ulcerative colitis. J Leukoc Biol 2008;84:1392–1399.
- Coppi LC, Thomazzi SM, de Ayrizono ML, Coy CS, Fagundes WJ, Goes JR, Franchi GC, Jr., Nowill AE, Montes CG, Antunes E, Ferraz JG: Comparative study of eosinophil chemotaxis, adhesion, and degranulation in vitro in ulcerative colitis and Crohn’s disease. Inflamm Bowel Dis 2007;13:211–218.
- Ahrens R, Waddell A, Seidu L, Blanchard C, Carey R, Forbes E, Lampinen M, Wilson T, Cohen E, Stringer K, Ballard E, Munitz A, Xu H, Lee N, Lee JJ, Rothenberg ME, Denson L, Hogan SP: Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis. J Immunol 2008;181:7390–7399.
- Bochner BS: Systemic activation of basophils and eosinophils: markers and consequences. J Allergy Clin Immunol 2000;106:S292–S302.
- Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS: Eosinophil’s role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 2003;167:199–204.
- Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID: Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973–984.
Received: April 5, 2011
Accepted after revision: August 2, 2011
Published online: September 13, 2011
Number of Print Pages : 11
Number of Figures : 4, Number of Tables : 3, Number of References : 40
Journal of Innate Immunity
Vol. 3, No. 6, Year 2011 (Cover Date: October 2011)
Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)
For additional information: http://www.karger.com/JIN
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.