Siglec-F is a
sialic acid-binding Ig superfamily receptor that is highly expressed on eosinophils. We have investigated whether administration of an anti-
Siglec-F Ab to OVA-challenged wild-type mice would reduce levels of eosinophilic
inflammation and levels of
airway remodeling. Mice sensitized to OVA and challenged repetitively with OVA for 1 mo who were administered an anti-
Siglec-F Ab had significantly reduced levels of peribronchial eosinophilic
inflammation and significantly reduced levels of subepithelial
fibrosis as assessed by either trichrome staining or lung
collagen levels. The anti-
Siglec-F Ab reduced the number of bone marrow, blood, and tissue eosinophils, suggesting that the anti-
Siglec-F Ab was reducing the production of eosinophils. Administration of a F(ab')(2) fragment of an anti-
Siglec-F Ab also significantly reduced levels of eosinophilic
inflammation in the lung and blood. FACS analysis demonstrated increased numbers of apoptotic cells (
annexin V(+)/CCR3(+) bronchoalveolar lavage and bone marrow cells) in anti-
Siglec-F Ab-treated mice challenged with OVA. The anti-
Siglec-F Ab significantly reduced the number of peribronchial major basic
protein(+)/
TGF-beta(+) cells, suggesting that reduced levels of eosinophil-derived
TGF-beta in anti-
Siglec-F Ab-treated mice contributed to reduced levels of peribronchial
fibrosis. Administration of the anti-
Siglec-F Ab modestly reduced levels of
periodic acid-Schiff-positive mucus cells and the thickness of the smooth muscle layer. Overall, these studies suggest that administration of an anti-
Siglec-F Ab can significantly reduce levels of
allergen-induced eosinophilic airway
inflammation and features of
airway remodeling, in particular subepithelial
fibrosis, by reducing the production of eosinophils and increasing the number of apoptotic eosinophils in lung and bone marrow.