title: 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 that regulate glucose metabolism. GLP-1 also has immune modulatory roles.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, Firestone Institute of Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: P D
authors.initials: PD
authors.lastname: Mitchell
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, Firestone Institute of Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: B M
authors.initials: BM
authors.lastname: Salter
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, Firestone Institute of Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: J P
authors.initials: JP
authors.lastname: Oliveria
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, Firestone Institute of Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: El-Gammal
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, Firestone Institute of Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Tworek
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, Firestone Institute of Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: S G
authors.initials: SG
authors.lastname: Smith
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, Firestone Institute of Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Sehmi
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, Firestone Institute of Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: G M
authors.initials: GM
authors.lastname: Gauvreau
authors.affiliation: Department of Medicine, University College Dublin, Dublin, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Butler
authors.affiliation: Department of Medicine, Michael G. DeGroote School of Medicine, Firestone Institute of Respiratory Health, McMaster University, Hamilton, ON, Canada.
authors.forename: P M
authors.initials: PM
authors.lastname: O'Byrne
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001985:Bronchial Provocation Tests; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D000067757:Glucagon-Like Peptide-1 Receptor / Q000235:genetics*; D006801:Humans; D056747:Immunomodulation / Q000235:genetics*; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D012129:Respiratory Function Tests; D055815:Young Adult
chemical_list: D000485:Allergens; D000067757:Glucagon-Like Peptide-1 Receptor; D016210:Methacholine Chloride
keywords: asthma; basic mechanisms; pharmacology and inhaled allergens