Allergic inflammation involves the mobilization and trafficking of eosinophils to sites of inflammation. Galectin-3 (Gal-3) has been shown to play a critical role in eosinophil recruitment and airway allergic inflammation in vivo. The role played by Gal-3 in human eosinophil trafficking was investigated. Eosinophils from allergic donors expressed elevated levels of Gal-3 and demonstrated significantly increased rolling and firm adhesion on immobilized VCAM-1 and, more surprisingly, on Gal-3 under conditions of flow. Inhibition studies with specific mAbs as well as lactose demonstrated that: 1) eosinophil-expressed Gal-3 mediates rolling and adhesion on VCAM-1; 2) alpha(4) integrin mediates eosinophil rolling on immobilized Gal-3; and 3) eosinophil-expressed Gal-3 interacts with immobilized Gal-3 through the carbohydrate recognition domain of Gal-3 during eosinophil trafficking. These findings were further confirmed using inflamed endothelial cells. Interestingly, Gal-3 was found to bind to alpha(4) integrin by ELISA, and the two molecules exhibited colocalized expression on the cell surface of eosinophils from allergic donors. These findings suggest that Gal-3 functions as a cell surface adhesion molecule to support eosinophil rolling and adhesion under conditions of flow.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.4049/jimmunol.179.11.7800 | DOI Listing |
Clin Exp Allergy
October 2023
Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
Background: Fungal sensitization (FS) exacerbates asthma in patients who have elevated type 2 inflammatory response. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases.
Objective: This post hoc analysis, funded by the manufacturers of dupilumab, was conducted to assess dupilumab efficacy in patients from the phase 3 LIBERTY ASTHMA QUEST trial (NCT02414854) and TRAVERSE open-label extension (NCT02134028) study who had uncontrolled, moderate-to-severe asthma with type 2 inflammatory phenotype (defined as blood eosinophil count ≥150 cells/μL or FeNO ≥25 ppb) and with FS (defined as IgE specific to Alternaria alternata, Aspergillus fumigatus or Cladosporium herbarum >0.
Allergy
August 2023
Regeneron Pharmaceuticals, Inc., Tarrytown, New York, USA.
Ann Allergy Asthma Immunol
July 2023
Department of Immunology, Sanofi, Bridgewater, New Jersey.
Background: Type 2 inflammation is common in children with asthma. Dupilumab, a human antibody, blocks the signaling of interleukin -4 and -13, key and central drivers of type 2 inflammation. In the LIBERTY ASTHMA VOYAGE (NCT02948959) study, dupilumab reduced severe asthma exacerbations and improved lung function in children aged 6 to 11 years with uncontrolled, moderate-to-severe asthma.
View Article and Find Full Text PDFVopr Pitan
September 2022
Scientific Research Institute of Medical Problems of the North of the Federal Research Center «Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences», 660022, Krasnoyarsk, Russian Federation.
Psoriasis (PS) is a multifactorial disease with a dominant role of genetic predisposition, but the questions of PS etiology and pathogenesis still remain open. The development of PS can be facilitated by environmental factors, as well as a violation of the skin barrier and immune imbalance. In the literature of recent years, an association in clinical practice between PS and atopic diseases (atopic dermatitis, bronchial asthma, allergic rhinitis) has been increasingly reported.
View Article and Find Full Text PDFBackground: Safety and efficacy data for dupilumab beyond 1 year are lacking for patients from Japan with moderate-to-severe asthma.
Methods: The TRAVERSE open-label extension (OLE) study (NCT02134028) assessed the safety and efficacy of dupilumab 300 mg every 2 weeks up to 96 weeks in 2282 patients who completed a previous dupilumab asthma study. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs).
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!