Anti-Siglec-F antibody inhibits oral egg allergen induced intestinal eosinophilic inflammation in a mouse model.
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 loss 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 lower 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.
Song
Dae Jin
DJ
Department of Medicine, University of California San Diego, San Diego, CA, USA.
Cho
Jae Youn
JY
Miller
Marina
M
Strangman
Wendy
W
Zhang
Mai
M
Varki
Ajit
A
Broide
David H
DH
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D054413:Chemokine CCL11 / Q000276:immunology; D004195:Disease Models, Animal; D021181:Egg Hypersensitivity / Q000276:immunology* / Q000628:therapy; D004802:Eosinophilia / Q000276:immunology*; D005260:Female; D005767:Gastrointestinal Diseases / Q000276:immunology* / Q000628:therapy; D006651:Histocytochemistry; D007073:Immunoglobulin E / Q000097:blood; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010865:Pilot Projects; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D018418:Th2 Cells / Q000276:immunology
D000906:Antibodies; D015214:Antigens, Differentiation, Myelomonocytic; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C443130:Siglecf protein, mouse; D007073:Immunoglobulin E