Therapeutic Effects of an Anti-sialyl Lewis X Antibody in a Murine Model of Allergic Asthma

• Published in: International journal of molecular sciences 2021-09, Vol.22 (18), p.9961
• Main Authors: Xiong, Wei, Liu, Wenxin, Nishida, Shogo, Komiyama, Daichi, Liu, Wei, Hirakawa, Jotaro, Kawashima, Hiroto
• Format: Article
• Language: English
• Subjects: Allergens; Allergies; Animal models; Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; antibody; Asthma; Asthma - complications; Asthma - drug therapy; Blood vessels; Bone marrow; Bone Marrow - pathology; Bronchus; Carbohydrates; Cell Differentiation; Chemokines; Class switching; Cytokines; Disease Models, Animal; druggable targets; Endothelial cells; Eosinophils - immunology; Female; Flow cytometry; Hypersensitivity - complications; Hypersensitivity - drug therapy; Immunity; Immunoglobulin E; Inflammation; leukocyte infiltration; Leukocytes (eosinophilic); Ligands; Lung - immunology; Lung - pathology; Lungs; Lymphocytes T; Mice; Mice, Inbred C57BL; Models, Biological; Monoclonal antibodies; Ovalbumin; P-selectin; P-Selectin - metabolism; Patients; Polysaccharides; Protein Binding; Proteins; Selectins; sialyl Lewis X; Sialyl Lewis x antigen; Sialyl Lewis X Antigen - immunology
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22189961

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 (sLe ) 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 sLe glycans, and their infiltration into the lungs and proliferation in the bone marrow were significantly suppressed by an anti-sLe 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 sLe 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 sLe carbohydrate antigen could serve as a novel therapeutic target for allergic asthma.