The alpha4bbeta7-integrin is dynamically expressed on murine eosinophils and involved in eosinophil trafficking to the intestine.
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.
Brandt
E B
EB
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Zimmermann
N
N
Muntel
E E
EE
Yamada
Y
Y
Pope
S M
SM
Mishra
A
A
Hogan
S P
SP
Rothenberg
M E
ME
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
D039641:Integrin beta Chains; D016023:Integrins; D015848:Interleukin-5; C071777:integrin alpha4beta7; C091368:integrin beta7; D039441:Integrin alpha4; D015847:Interleukin-4