The α4β7-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 alpha 4-integrin has been identified as critically involved in eosinophil trafficking in the lung. Most studies have focused on the role of the alpha 4 beta 1-adhesion complex, but eosinophils also express the alpha 4 beta 7-integrin complex. Objective To investigate the role of alpha 4 beta 7, 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 beta 7-integrin deficiency on eosinophil recruitment to the lungs and intestine in specific experimental allergic models. Results Evaluation of alpha 4 beta 7 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 alpha 4 beta 7-complex. While expression of the alpha 4-chain remained unchanged, a significant decrease in beta 7-surface expression was observed. Intestinal eosinophils, isolated from Peyer's patches, also displayed a down-regulation of the alpha 4 beta 7-integrin, albeit only modest. In contrast, circulating eosinophils, isolated from the blood and spleen, expressed high levels of the alpha 4 beta 7-integrin. However, eosinophil trafficking into the lungs of beta 7-integrin-deficient mice was not significantly impaired in response to respiratory allergen challenges. In contrast, beta 7-deficient mice had impaired eosinophil recruitment to the intestine. Conclusion Taken together, these results identify differential expression of the alpha 4 beta 7-integrin on eosinophils and its critical role in regulating eosinophil responses in the intestine.