Interferon-Gamma Induces lnterleukin-3 Release from Peripheral Blood Eosinophils

Fujisawa, Takao; Fukuda, Setsuya; Atsuta, Jun; Ichimi, Ryouji; Kamiya, Hitoshi; Sakurai, Minami A.

doi:10.1159/000236748

Cited by 22 publications

(7 citation statements)

References 8 publications

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“…The first two mechanisms are the most commonly observed in tissue biopsies from subjects with eosinophilic inflammation. A number of physiological agonists may induce the release of eosinophil granule proteins, for example, serum-opsonized surfaces [20], alternative complement factor C5a [21], immunoglobulin complexes [22] and cytokines including IL-3, IL-5, granulocyte/macrophage colony-stimulating factor (GM-CSF) and IFN [11, [23][24][25][26]. The current thinking is that much of the airway damage associated with asthma and allergic inflammation may be related to the release of eosinophil granule proteins MBP, EPO and ECP [27][28][29][30].…”

Section: Eosinophilsmentioning

confidence: 99%

Eosinophil Cytokines

Lacy¹,

Moqbel²

2000

Chemical Immunology and Allergy

110

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Eosinophils are major effector cells in helminthic parasite immunity as well as in allergic inflammation. These highly granulated cells are generally found at extremely low densities within mucosal tissues, and are recruited from the bloodstream to inflammatory foci during a range of immune and allergic responses. The recruitment and accumulation of eosinophils within mucosal tissues is thought to be the result of regulation by a complex series of events involving antigen presenting cells, mast cells, T-cells, B-cells and their released cytokines and chemokines.More recently, it has been discovered that eosinophils themselves are a source of cytokines, chemokines and growth factors, which may have profound influences on the progression of the allergic inflammatory response ( fig. 1). The purpose of this review is to examine the role that eosinophil-derived cytokines, chemokines and growth factors may have in the propagation or exacerbation of the allergic response. For simplicity, the word 'cytokine' will be used to describe the collective group of cytokines, growth factors and chemokines in this review. Cytokines in Allergic Inflammation and AsthmaAllergic inflammation and asthma are characterized by acute or chronic inflammatory cell infiltration into sites of allergen exposure in atopic subjects. In asthma, activated inflammatory cells, including eosinophils, are thought to be directly involved in initiating and/or maintaining bronchoconstriction, mucus secretion, edema and tissue injury within the airways. The inflammatory processes underlying allergic inflammation are governed by an elaborate cyto-

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Section: Eosinophilsmentioning

confidence: 99%

Eosinophil Cytokines

Lacy¹,

Moqbel²

2000

Chemical Immunology and Allergy

110

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“…Other more recently indicated functions of eosinophils are based on their capacity to release cytokines (1,4). Since the first report of human eosinophils as a cytokine source by our group (6), these cells are now known to synthesize numerous cytokines with multiple biologic activities including transforming growth factor‐α (TGF‐α) (6), granulocyte macrophage colony‐stimulating factor (GM‐CSF) (7), tumor necrosis factor‐α (TNF‐α) (8), interleukin (IL)‐3 (9), IL‐5 (10), IL‐4 (11), IL‐16 (12), regulated on activation, normal, T‐cell expressed and secreted (RANTES) (13), vascular endothelial growth factor (VEGF) (14), stem cell factor (SCF) (15) and IL‐13 (16). Both cytokines and distinct eosinophil cationic proteins (ECPs) are stored in preformed pools within eosinophil specific granules and can be released upon stimulation (3,5,17).…”

mentioning

confidence: 99%

Intragranular Vesiculotubular Compartments are Involved in Piecemeal Degranulation by Activated Human Eosinophils

Melo

Perez

Spencer

et al. 2005

Traffic

165

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Eosinophils, leukocytes involved in allergic, inflammatory and immunoregulatory responses, have a distinct capacity to rapidly secrete preformed granule-stored proteins through piecemeal degranulation (PMD), a secretion process based on vesicular transport of proteins from within granules for extracellular release. Eosinophil-specific granules contain cytokines and cationic proteins, such as major basic protein (MBP). We evaluated structural mechanisms responsible for mobilizing proteins from within eosinophil granules. Human eosinophils stimulated for 30-60 min with eotaxin, regulated on activation, normal, T-cell expressed and secreted (RANTES) or platelet activating factor exhibited ultrastructural features of PMD (e.g. losses of granule contents) and extensive vesiculotubular networks within emptying granules. Brefeldin A inhibited granule emptying and collapsed intragranular vesiculotubular networks. By immunonanogold ultrastructural labelings, CD63, a tetraspanin membrane protein, was localized within granules and on vesicles outside of granules, and mobilization of MBP into vesicles within and extending from granules was demonstrated. Electron tomography with three dimension reconstructions revealed granule internal membranes to constitute an elaborate tubular network able to sequester and relocate granule products upon stimulation. We provide new insights into PMD and identify eosinophil specific granules as organelles whose internal tubulovesicular networks are important for the capacity of eosinophils to secrete, by vesicular transport, their content of preformed and granule-stored cytokines and cationic proteins.

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“…6 The effect of IFN␥ on stimulating the release of other eosinophil-derived cytokines and chemokines has also been observed. [13][14][15] IFN␥ is a cytokine described as the prominent product of Th1-type lymphocytes in both mouse and human, 16,17 and is usually associated with a wide range of bacterial and viral infections. Serum levels of IFN␥ have been shown to be elevated in acute severe asthma.…”

mentioning

confidence: 99%

Intracellular Localization of Interleukin-6 in Eosinophils From Atopic Asthmatics and Effects of Interferon γ

Lacy

Levi‐Schaffer

Mahmudi‐Azer

et al. 1998

Blood

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Eosinophils, prominent cells in asthmatic inflammation, have been shown to synthesize, store, and release an array of up to 18 cytokines and growth factors, including interleukin-6 (IL-6). In this report, we show that IL-6 immunofluorescence localizes to the matrix of the crystalloid granule in peripheral blood eosinophils from atopic asthmatics using confocal laser scanning microscopy (CLSM). Granule localization of IL-6 was confirmed using dot-blot analysis and enzyme-linked immunosorbent assay (ELISA) on subcellular fractions of highly purified eosinophils produced from density centrifugation across a 0% to 45% Nycodenz gradient. IL-6 was found to coelute with eosinophil crystalloid granule marker proteins, including eosinophil peroxidase (EPO), major basic protein (MBP), arylsulfatase B, and β-hexosaminidase. Immunoreactivity to IL-6 colocalized with granule-associated IL-2 and IL-5 in subfractionated eosinophils. We also made the novel and compelling observation that interferon γ (IFNγ), a Th1-type cytokine, stimulated an early elevation in eosinophil IL-6 immunoreactivity. A 2.5-fold enhancement of IL-6 immunoreactivity in eosinophil granules was observed within 10 minutes of IFNγ treatment (500 U/mL), as determined by subcellular fractionation and CLSM. These findings suggest that IFNγ has short-term effects on human eosinophil function and imply that a physiologic role exists for Th1-type cytokine modulation of Th2-type responses in these cells.

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Interferon-Gamma Induces lnterleukin-3 Release from Peripheral Blood Eosinophils

Cited by 22 publications

References 8 publications

Eosinophil Cytokines

Eosinophil Cytokines

Intragranular Vesiculotubular Compartments are Involved in Piecemeal Degranulation by Activated Human Eosinophils

Intracellular Localization of Interleukin-6 in Eosinophils From Atopic Asthmatics and Effects of Interferon γ

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