title: The alpha4bbeta7-integrin is dynamically expressed on murine eosinophils and involved in eosinophil trafficking to the intestine.
abstract: BACKGROUND
  Of the numerous adhesion molecules expressed by eosinophils, the alpha4-integrin has been identified as critically involved in eosinophil trafficking in the lung. Most studies have focused on the role of the alpha4beta1-adhesion complex, but eosinophils also express the alpha4beta7-integrin complex.
  
  
  OBJECTIVE
  To investigate the role of alpha4beta7, by assessing its membrane expression on eosinophils from different compartments using allergen-challenged mice and IL-4/IL-5 bi-transgenic mice. In addition, we aim to determine the impact of beta7-integrin deficiency on eosinophil recruitment to the lungs and intestine in specific experimental allergic models.
  
  
  RESULTS
  Evaluation of alpha4beta7 expression on bronchoalveolar lavage fluid (BALF) and lung tissue eosinophils revealed a down-regulation of this integrin as eosinophils migrate through the lungs. Indeed eosinophils isolated from the BALF and lung of allergic mice had low expression of the alpha4beta7-complex. While expression of the alpha4-chain remained unchanged, a significant decrease in beta7-surface expression was observed. Intestinal eosinophils, isolated from Peyer's patches, also displayed a down-regulation of the alpha4beta7-integrin, albeit only modest. In contrast, circulating eosinophils, isolated from the blood and spleen, expressed high levels of the alpha4beta7-integrin. However, eosinophil trafficking into the lungs of beta7-integrin-deficient mice was not significantly impaired in response to respiratory allergen challenges. In contrast, beta7-deficient mice had impaired eosinophil recruitment to the intestine.
  
  
  CONCLUSIONS
  Taken together, these results identify differential expression of the alpha4beta7-integrin on eosinophils and its critical role in regulating eosinophil responses in the intestine.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Brandt
authors.forename: N
authors.initials: N
authors.lastname: Zimmermann
authors.forename: E E
authors.initials: EE
authors.lastname: Muntel
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: S M
authors.initials: SM
authors.lastname: Pope
authors.forename: A
authors.initials: A
authors.lastname: Mishra
authors.forename: S P
authors.initials: SP
authors.lastname: Hogan
authors.forename: M E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D004804:Eosinophils / Q000276:immunology*; D039441:Integrin alpha4 / Q000276:immunology; D039641:Integrin beta Chains / Q000276:immunology; D016023:Integrins / Q000032:analysis*; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D007422:Intestines / Q000166:cytology* / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010581:Peyer's Patches / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D039641:Integrin beta Chains; D016023:Integrins; D015848:Interleukin-5; C071777:integrin alpha4beta7; C091368:integrin beta7; D039441:Integrin alpha4; D015847:Interleukin-4