α4 integrin‐dependent eosinophil recruitment in allergic but not non‐allergic inflammation

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Abstract
Although anti‐α4 integrin mAbs reduce eosinophil accumulation in several models of allergic inflammation, it is not clear whether this occurs via a direct action to block eosinophil α4 integrins or indirectly on another cell type. The role of α4 integrins on the accumulation of 111In‐labelled eosinophils in allergic and non‐allergic inflammation in guinea‐pig skin was therefore investigated. Intradermal injection of antigen in sensitized skin sites induced accumulation of 111In‐eosinophils that was reduced up to 70% by two anti‐α4 integrin mAbs. In contrast, accumulation of 111In‐eosinophils to intradermal chemoattractants was unaffected by the same mAbs. Accumulation of 111In‐eosinophils in allergic and non‐allergic conditions was partly inhibited by a low dose of an anti‐β2 integrin mAb. In combination with anti‐α4 integrin mAb, responses were not further reduced suggesting that these adhesion pathways are not additive or synergic. Pretreating skin sites with antiserum or contaminating LPS did not reveal an α4 integrin dependent pathway for chemoattractant‐induced 111In‐eosinophil accumulation. These data suggest that α4 integrins are involved in the response to antigen in sensitized skin sites. Pretreating 111In‐eosinophil with α4 integrin mAb blocked their adhesion to fibronectin in vitro but did not inhibit their accumulation in allergic inflammation suggesting that the blocking effect in vivo was eosinophil independent. These data support the concept that targeting α4 integrins on cells other than eosinophils could control eosinophil accumulation and have therapeutic potential in allergic diseases such as asthma and atopic dermatitis. British Journal of Pharmacology (2001) 132, 596–604; doi:10.1038/sj.bjp.0703857

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