Abstract
Asthma is an allergic disease that causes severe infiltration of leukocytes into the lungs. Leukocyte infiltration is mediated by the binding of sialyl Lewis X (sLex) glycans present on the leukocytes to E-and P-selectins present on the endothelial cells at the sites of inflammation. Here, we found that mouse eosinophils express sLex glycans, and their infiltration into the lungs and proliferation in the bone marrow were significantly suppressed by an anti-sLex monoclonal antibody (mAb) F2 in a murine model of ovalbumin-induced asthma. The percentage of eosinophils in the bronchoalveolar lavage fluid and bone marrow and serum IgE levels decreased significantly in the F2-administered mice. Levels of T helper type 2 (Th2) cytokines and chemokines, involved in IgE class switching and eosinophil proliferation and recruitment, were also decreased in the F2-administered mice. An ex vivo cell rolling assay revealed that sLex glycans mediate the rolling of mouse eosinophils on P-selectin-expressing cells. These results indicate that the mAb F2 exerts therapeutic effects in a murine model of allergen-induced asthma, suggesting that sLex carbohydrate antigen could serve as a novel therapeutic target for allergic asthma.
Highlights
Bronchial asthma is the most common chronic airway disease with over 250 million patients worldwide [1]
To explore whether sialyl Lewis X (sLex) could be a target for the treatment of allergic asthma, we investigated the expression of sLex in mouse eosinophils using the monoclonal antibody (mAb) F2 and examined its therapeutic effects in a murine model of allergen-induced asthma
Asthma was first induced in WT mice and FucT-IV/VII DKO mice lacking sLex glycans
Summary
Bronchial asthma is the most common chronic airway disease with over 250 million patients worldwide [1]. Based on the abovementioned mechanisms for leukocyte infiltration, we hypothesized that targeting sLex , the ligand for P- and E-selectin, with specific anti-glycan antibodies would be a potential therapy for asthma. Administration of F2 into mice significantly blocked lymphocyte homing to peripheral lymph nodes and suppressed leukocyte infiltration in a murine contact hypersensitivity model. Based on these findings, we hypothesized that mAb F2 should have therapeutic effects against asthma. To explore whether sLex could be a target for the treatment of allergic asthma, we investigated the expression of sLex in mouse eosinophils using the mAb F2 and examined its therapeutic effects in a murine model of allergen-induced asthma
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