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

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.
AuthorsWei Xiong, Wenxin Liu, Shogo Nishida, Daichi Komiyama, Wei Liu, Jotaro Hirakawa, Hiroto Kawashima
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 18 (Sep 15 2021) ISSN: 1422-0067 [Electronic] Switzerland
PMID34576124 (Publication Type: Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • P-Selectin
  • Sialyl Lewis X Antigen
Topics
  • Animals
  • Antibodies, Monoclonal (administration & dosage, therapeutic use)
  • Asthma (complications, drug therapy)
  • Bone Marrow (pathology)
  • Cell Differentiation
  • Disease Models, Animal
  • Eosinophils (immunology)
  • Female
  • Hypersensitivity (complications, drug therapy)
  • Immunity
  • Lung (immunology, pathology)
  • Mice, Inbred C57BL
  • Models, Biological
  • P-Selectin (metabolism)
  • Protein Binding
  • Sialyl Lewis X Antigen (immunology)
  • Mice

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