Glucagon‐like peptide‐1 receptor expression on human eosinophils and its regulation of eosinophil activation

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Abstract
Summary: Background: Glucagon‐like peptide‐1 (GLP‐1) and its receptor are part of the incretin family of hormones that regulate glucose metabolism. GLP‐1 also has immune modulatory roles.Objectives: To measure the expression of the GLP‐1 receptor (GLP‐1R) on eosinophils and neutrophils in normal and asthmatic subjects and evaluate effects of a GLP‐1 analog on eosinophil function.Methods: Peripheral blood samples were taken from 10 normal and 10 allergic asthmatic subjects. GLP‐1R expression was measured on eosinophils and neutrophils. Subsequently, the asthmatic subjects underwent allergen and diluent inhalation challenges, and GLP‐1R expression was measured. Purified eosinophils, collected from mild asthmatic subjects, were stimulated with lipopolysaccharide (LPS) and a GLP‐1 analog to evaluate eosinophil cell activation markers CD11b and CD69 and cytokine (IL‐4, IL‐5, IL‐8 and IL‐13) production.Results: Glucagon‐like peptide‐1 receptor is expressed on human eosinophils and neutrophils. Eosinophil, but not neutrophil, expression of GLP‐1R is significantly higher in normal controls compared to allergic asthmatics. The expression of GLP‐1R did not change on either eosinophils or neutrophils following allergen challenge. A GLP‐1 analog significantly decreased the expression of eosinophil‐surface activation markers following LPS stimulation and decreased eosinophil production of IL‐4, IL‐8 and IL‐13, but not IL‐5.Conclusion and Clinical Relevance: Glucagon‐like peptide‐1 receptor is expressed on human eosinophils and neutrophils. A GLP‐1 analog attenuates LPS‐stimulated eosinophil activation. GLP‐1 agonists may have additional adjunctive indications in treating persons with concomitant type 2 diabetes mellitus and asthma.

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