期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 18, 页码 -出版社
MDPI
DOI: 10.3390/ijms22189961
关键词
druggable targets; sialyl Lewis X; antibody; asthma; leukocyte infiltration
资金
- Japan Agency for Medical Research and Development (AMED) [20ae0101034h0005]
- JSPS KAKENHI [20H03379, 15K18869]
- Institute for Global Prominent Research of Chiba University
- Japan Allergy Foundation
- SENSHIN Medical Research Foundation
- Hamaguchi Foundation for the Advancement of Biochemistry
- Kobayashi International Foundation
- Mizutani Foundation for Glycoscience
- Kato Memorial Bioscience Foundation
- Grants-in-Aid for Scientific Research [20H03379, 15K18869] Funding Source: KAKEN
Asthma is an allergic disease characterized by severe leukocyte infiltration in the lungs, which can be significantly suppressed by the anti-sLe(x) monoclonal antibody F2, leading to reduced eosinophil infiltration, proliferation, serum IgE levels, as well as levels of Th2 cytokines and chemokines. The study suggests that sLe(x) carbohydrate antigen could be a novel therapeutic target for allergic asthma.
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(x)) 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(x) glycans, and their infiltration into the lungs and proliferation in the bone marrow were significantly suppressed by an anti-sLe(x) 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(x) 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(x) carbohydrate antigen could serve as a novel therapeutic target for allergic asthma.
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