Mechanisms of eosinophil-associated inflammation

Gleich, Gerald J.

doi:10.1067/mai.2000.105712

Cited by 695 publications

(535 citation statements)

References 100 publications

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“…At sites of allergic inflammation, activated eosinophils cause tissue damage by the production of reactive oxygen species (ROS) and the release of toxic granule proteins 36. To explore the impact of selective CB 2 activation on eosinophil respiratory burst, purified human eosinophils were applied to 250 nM JWH‐133 for 5 min at 37°C and respiratory burst was induced with eotaxin‐2/CCL24.…”

Section: Resultsmentioning

confidence: 99%

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen‐induced pulmonary inflammation in mice

Frei

Luschnig

Parzmair

et al. 2016

Allergy

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BackgroundAccumulation of activated eosinophils in tissue is a hallmark of allergic inflammation. The endocannabinoid 2‐arachidonoylglycerol (2‐AG) has been proposed to elicit eosinophil migration in a CB 2 receptor/Gi/o‐dependent manner. However, it has been claimed recently that this process may also involve other mechanisms such as cytokine priming and the metabolism of 2‐AG into eicosanoids. Here, we explored the direct contribution of specific CB 2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo.Methods In vitro studies including CB 2 expression, adhesion and migratory responsiveness, respiratory burst, degranulation, and calcium mobilization were conducted in human peripheral blood eosinophils and mouse bone marrow‐derived eosinophils. Allergic airway inflammation was assessed in mouse models of acute OVA‐induced asthma and directed eosinophil migration.Results CB 2 expression was significantly higher in eosinophils from symptomatic allergic donors. The selective CB 2 receptor agonist JWH‐133 induced a moderate migratory response in eosinophils. However, short‐term exposure to JWH‐133 potently enhanced chemoattractant‐induced eosinophil shape change, chemotaxis, CD11b surface expression, and adhesion as well as production of reactive oxygen species. Receptor specificity of the observed effects was confirmed in eosinophils from CB 2 knockout mice and by using the selective CB 2 antagonist SR144528. Of note, systemic application of JWH‐133 clearly primed eosinophil‐directed migration in vivo and aggravated both AHR and eosinophil influx into the airways in a CB 2‐specific manner. This effect was completely absent in eosinophil‐deficient ∆dblGATA mice.ConclusionOur data indicate that CB 2 may directly contribute to the pathogenesis of eosinophil‐driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB 2‐mediated priming of eosinophils. Hence, antagonism of CB 2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders.

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Section: Resultsmentioning

confidence: 99%

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen‐induced pulmonary inflammation in mice

Frei

Luschnig

Parzmair

et al. 2016

Allergy

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“…As effector cells eosinophils, based in part on their release of cationic granule proteins and lipid mediators, may contribute to the immunopathogenesis of allergic diseases (1). Additional functional roles for eosinophils are indicated by findings that eosinophils may exert immunomodulatory activities via interactions with T and B lymphocytes.…”

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confidence: 99%

Cutting Edge: Eotaxin Elicits Rapid Vesicular Transport-Mediated Release of Preformed IL-4 from Human Eosinophils

Bandeira‐Melo

Sugiyama

Woods

et al. 2001

The Journal of Immunology

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IL-4 release is important in promoting Th2-mediated allergic and parasitic immune responses. Although human eosinophils are potential sources of IL-4, physiologic mechanisms to elicit its release have not been established. By flow cytometry and microscopy, eosinophils from normal donors uniformly contained preformed IL-4. In contrast to cytolytic IL-4 release from calcium ionophore-activated eosinophils, eotaxin and RANTES, but not IFN-γ, elicited IL-4 release by noncytotoxic mechanisms. With a dual Ab capture and detection immunofluorescent microscopic assay, IL-4 was released at discrete cell surface sites. IL-5 enhanced eotaxin-induced IL-4 release, which was mediated by G protein-coupled CCR3 receptors, detectable as early as 5 min and maximum within 1 h. IL-4 release was not diminished by transcription or protein synthesis inhibitors, but was suppressed by brefeldin A, an inhibitor of vesicle formation. Thus, CCR3-mediated signaling can rapidly mobilize IL-4 stored preformed in human eosinophils for release by vesicular transport to contribute to immune responses.

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“…Many studies have demonstrated a strong association between airway eosinophilic inflammations and the development of lung pathology observed in asthma (6). Eosinophilic inflammation in asthma is considered the major contributor to the structural changes in the airways of individuals with chronic asthma, including fibrosis, thickening of the airway smooth muscle layer due to hypertrophy, and hyperplasia of goblet cells (7,8). A major player in contributing to eosinophilia in asthma is the hypersecretion of IL-5 (9).…”

mentioning

confidence: 99%

Increased Expression and Activation of CD30 Induce Apoptosis in Human Blood Eosinophils

Berro

Perry

Agrawal

2004

The Journal of Immunology

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Eosinophils are one of the major effector cells in asthma, and controlling the number and survival of eosinophils might attenuate the severity of asthma. This result could be achieved by inducing eosinophil apoptosis. Apoptosis allows the removal of cells without inducing an inflammatory response. Our knowledge of the factors involved in regulating eosinophil apoptosis remains limited. CD30 molecule has been associated with T cell-negative selection and in TCR-mediated apoptosis. In this study we examined the expression and role of CD30 in apoptosis of human blood eosinophils. Percentage of apoptotic eosinophils was determined by annexin V-propidium iodide labeling, and CD30 expression was examined by flow cytometry. Spontaneous apoptosis was induced by serum deprivation, and survival was conferred by incubating cells with 10% FBS and IL-5. CD30 surface expression was up-regulated in eosinophils incubated for 24 h as compared with freshly isolated eosinophils, and both CD30 expression and eosinophil apoptosis increased in a time-dependent manner. We also measured CD30 mRNA expression by quantitative real-time RT-PCR and determined that CD30 transcripts increased in eosinophils undergoing apoptosis only under serum deprivation conditions. The agonistic CD30 Abs, Ber-H8 and HeFi-1, significantly enhanced eosinophil apoptosis. FBS and IL-5 failed to inhibit or suppress the CD30 agonistic-induced apoptosis. These data support the role of CD30 activation in eosinophil apoptosis. This research will help in furthering our understanding of eosinophil apoptosis and therefore might contribute to the development of better therapeutic modalities in the treatment and/or cure of allergic inflammation in bronchial asthma.

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Mechanisms of eosinophil-associated inflammation

Cited by 695 publications

References 100 publications

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen‐induced pulmonary inflammation in mice

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen‐induced pulmonary inflammation in mice

Cutting Edge: Eotaxin Elicits Rapid Vesicular Transport-Mediated Release of Preformed IL-4 from Human Eosinophils

Increased Expression and Activation of CD30 Induce Apoptosis in Human Blood Eosinophils

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