Anti-Siglec-F antibody inhibits oral egg allergen induced intestinal eosinophilic inflammation in a mouse model

Abstract

Siglec-F is a sialic acid binding immunoglobulin-superfamily receptor that is highly expressed on eosinophils. We have used a mouse model. of oral egg ovalbumin (OVA)-induced eosinophilic inflammation of the gastro-intestinal mucosa associated with diarrhea and weight toss to determine whether administering an anti-Siglec-F antibody would reduce levels of intestinal mucosal eosinophilic inflammation. Mice administered the anti-Siglec-F antibody had significantly tower levels of intestinal eosinophilic inflammation, and this was associated with reduced intestinal permeability changes, normalization of intestinal villous crypt height, and restoration of weight gain. The reduced numbers of intestinal eosinophils in anti-Siglec-F antibody treated mice was associated with significantly reduced numbers of bone marrow and peripheral blood eosinophils, but was not associated with significant changes in the numbers of proliferating or apoptotic jejunal eosinophils. In addition, the anti-Siglec-F Ab reduced Th2 cytokines and IgE levels. Overall, these studies demonstrate that administration of an anti-Siglec-F antibody significantly reduces levels of eosinophilic inflammation in the intestinal mucosa and that this was associated with reduced intestinal permeability changes, normalization of intestinal villous crypt height, and restoration of weight gain. (C) 2008 Elsevier Inc. All rights reserved.