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

Mitchell, Patrick; Salter, Brittany; Oliveria, John Paul; El-Gammal, Amani; Tworek, Damian; Smith, Steven G; Sehmi, Roma; Gauvreau, Gail M.; Butler, Marcus W.; O'Byrne, Paul M.

doi:10.1111/cea.12860

Cited by 45 publications

(37 citation statements)

References 34 publications

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“…The activation of eosinophils in inflammatory processes and immune response against helminths is regulated by interleukins IL-4, IL-8, IL-13 and TNF-α (Horrigan et al 2004, Ciepiela et al 2015. Additionally, some receptors are differentially expressed between eosinophils and neutrophils, such as the glucagon-like peptide 1 receptor (GLP-1R) (Mitchell et al 2017) and adenosine A3 receptor (A A3 R) (Ezeamuzie Table 1. Means (± standard error) of feed intake, weight gain and feed conversion of lambs fed different levels of inclusion of coffee pulp in the diet.…”

Section: Resultsmentioning

confidence: 99%

Health status and productivity of sheep fed coffee pulp during fattening

Bautista

Rodríguez-Magadán²,

Villegas-Sánchez

et al. 2018

Austral j. vet. sci.

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ABSTRACT. The objective of this study was to evaluate the productivity and health of fattening lambs fed different levels of coffee pulp in their diets. Thirty-five crossbred lambs with an average weight of 21.8 kg were fed isoproteic and isoenergetic diets with different percentages of coffee pulp (T0: control; T1: 7%; T2: 14%, T3: 21% and T4: 28%), the base diet was formulated with corn, soybean meal, alfalfa stubble, molasses, urea and mineral salt. The fattening period was 98 days. Productivity was measured by weight gain, feed intake and feed conversion. At the beginning and end of the study, blood samples were taken to determine the health status using a biochemical profile and blood count. Analysis of variance was performed using the initial weight as the covariate for the productive variables and the initial values of the analytes in the blood chemistry and hematological analysis tests. The coffee pulp did not affect productivity, although the amount of neutrophils decreased (P<0.05) as the coffee pulp in the diet increased. In all treatments, urea exceeded the reference values, whereas creatinine was below the reference values. We concluded that the inclusion of up to 28% coffee pulp in the diet did not affect the productive parameters, decreases the neutrophil count without affect health status of lambs during fattening.

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Section: Resultsmentioning

confidence: 99%

Health status and productivity of sheep fed coffee pulp during fattening

Bautista

Rodríguez-Magadán²,

Villegas-Sánchez

et al. 2018

Austral j. vet. sci.

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“…One recent example of such a factor that may regulate eosinophil activation is glucagon-like peptide (GLP)-1, a member of the incretin family of hormones, which regulates glucose metabolism (47). A GLP-1 analog inhibited upregulation of α M integrin and CD69 in vitro in response to lipopolysaccharide (47). Further, expression of GLP-1 receptor was lower on blood eosinophils in patients with allergic asthma than in normal controls (Table 1).…”

Section: Eosinophil Surface Proteins Altered After Antigen Challengementioning

confidence: 99%

“…The lower level of GLP-1R in asthma than in healthy subjects indicates that the eosinophil response to activating stimuli may be more regulated by GLP-1 in healthy persons and that eosinophil activation may be more easily achieved in asthma than in health. Further, Mitchell and colleagues suggest that GLP-1 agonists may have additional indications in treating patients with concomitant type 2 diabetes mellitus and asthma (47). …”

Section: Eosinophil Surface Proteins Altered After Antigen Challengementioning

confidence: 99%

Eosinophil Activation Status in Separate Compartments and Association with Asthma

Johansson

2017

Front. Med.

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Asthma is frequently characterized by eosinophil-rich airway inflammation. Airway eosinophilia is associated with asthma exacerbations and likely plays a part in airway remodeling. Eosinophil recruitment from the bloodstream depends on circulating eosinophils becoming activated, which leads to eosinophil arrest on activated endothelium, extravasation, and continued movement through the bronchial tissue by interaction with the extracellular matrix (ECM). Circulating eosinophils can exist at different activation levels, which include non-activated or pre-activated (sensitized or “primed”). Further, the bloodstream may lack pre-activated cells, due to such eosinophils having arrested on endothelium or extravasated into tissue. Increased expression, and in some instances, decreased expression of cell-surface proteins, including CD44, CD45, CD45R0, CD48, CD137, neuropeptide S receptor, cytokine receptors, Fc receptors, and integrins (receptors mediating cell adhesion and migration by interacting with ligands on other cells or in the ECM), and activated states of integrins or Fc receptors on blood eosinophils have been reported to correlate with aspects of asthma. A subset of these proteins has been reported to respond to intervention, e.g., with anti-interleukin (IL)-5. How these surface proteins and the activation state of the eosinophil respond to other interventions, e.g., with anti-IL-4 receptor alpha or anti-IL-13, is unknown. Eosinophil surface proteins suggested to be biomarkers of activation, particularly integrins, and reports on correlations between eosinophil activation and aspects of asthma are described in this review. Intermediate activation of beta1 and beta2 integrins on circulating eosinophils correlates with decreased pulmonary function, airway inflammation, or airway lumen eosinophils in non-severe asthma. The correlation does not appear in severe asthma, likely due to a higher degree of extravasation of pre-activated eosinophils in more severe disease. Bronchoalveolar lavage (BAL) eosinophils have highly activated integrins and other changes in surface proteins compared to blood eosinophils. The activation state of eosinophils in lung tissue, although likely very important in asthma, is largely unknown. However, some recent articles, mainly on mice but partly on human cells, indicate that tissue eosinophils may have a surface phenotype(s) different from that of sputum or BAL eosinophils.

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“…In the latest human study, Mitchell et al evaluated GLP-1R expression and GLP-1 effects on eosinophils and neutrophils of normal and allergic asthmatic subjects (Mitchell et al, 2016). While both cell types expressed the receptor, expression was significantly higher in controls compared to asthmatics.…”

Section: Therapeutic Benefits Of Glp-1 In Asthmamentioning

confidence: 99%

Glucagon-like peptide 1: A potential anti-inflammatory pathway in obesity-related asthma

Nguyen

Linderholm

Haczku

et al. 2017

Pharmacology & Therapeutics

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Alterations in arginine metabolism and accelerated formation of advanced glycation end-products (AGEs), crucial mechanisms in obesity-related asthma, can be modulated by glucagon-like peptide 1 (GLP-1). L-arginine dysregulation in obesity promotes inflammation and bronchoconstriction. Prolonged hyperglycemia, dyslipidemia, and oxidative stress leads to production of AGEs, that bind to their receptor (RAGE) further potentiating inflammation. By binding to its widely distributed receptor, GLP-1 blunts the effects of RAGE activation and arginine dysregulation. The GLP-1 pathway, while comprehensively studied in the endocrine and cardiovascular literature, is under-recognized in pulmonary research. Insights into GLP-1 and the lung may lead to novel treatments for obesity-related asthma.

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

Abstract: 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.

Cited by 45 publications

References 34 publications

Health status and productivity of sheep fed coffee pulp during fattening

Health status and productivity of sheep fed coffee pulp during fattening

Eosinophil Activation Status in Separate Compartments and Association with Asthma

Glucagon-like peptide 1: A potential anti-inflammatory pathway in obesity-related asthma

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