Glucagon Like Peptide-1 receptor expression on human eosinophils and its regulation of eosinophil activation

Abstract

Background

Glucagon Like Peptide-1 (GLP-1) and its receptor are part of the incretin family of hormones the 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 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

GLP-1R 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 & Clinical Relevance

GLP-1R 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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