The role of reactive oxygen species and nitric oxide in mast cell‐dependent inflammatory processes

Swindle, Emily J.; Metcalfe, Dean D.

doi:10.1111/j.1600-065x.2007.00513.x

Cited by 189 publications

(147 citation statements)

References 157 publications

(197 reference statements)

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“…However, it is known that low levels of ROS serve as second messengers in mast cell signaling, leading to degranulation, eicosanoid production, and cytokine secretion [16]. In this view, DJ-1 seems to mediate such "ROS-dependent signaling" in mast cells.…”

Section: Lyn-sykmentioning

confidence: 99%

Mast cell activation: A complex interplay of positive and negative signaling pathways

Sibilano¹,

2014

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Mast cells regulate the immunological responses causing allergy and autoimmunity, and contribute to the tumor microenvironment through generation and secretion of a broad array of preformed, granule-stored and de novo synthesized bioactive compounds. The release and production of mast cell mediators is the result of a coordinated signaling machinery, followed by the FcεRI and FcγR antigen ligation. In this review, we present the latest understanding of FcεRI and FcγR signaling, required for the canonical mast cell activation during allergic responses and anaphylaxis. We then describe the cooperation between the signaling of FcR and other recently characterized membrane-bound receptors (i.e., IL-33R and thymic stromal lymphopoietin receptor) and their role in the chronic settings, where mast cell activation is crucial for the development and the sustainment of chronic diseases, such as asthma or airway inflammation. Finally, we report how the FcR activation could be used as a therapeutic approach to treat allergic and atopic diseases by mast cell inactivation. Understanding the magnitude and the complexity of mast cell signaling is necessary to identify the mechanisms underlying the potential effector and regulatory roles of mast cells in the biology and pathology of those disease settings in which mast cells are activated.Keywords: FcεRI r FcγR r IL-33 r mast cells r TSLP IntroductionMast cells originate in the BM from a lineage-specific multipotent hematopoietic progenitor, circulate as CD34 + precursors until they migrate to tissues and mature into effector cells in the proximity of organs and blood vessels. Mast cells respond to antigenic stimulation through the cross-linking of immunoglobulin E (IgE) bound to high-affinity receptors for IgE (FcεRI) and the activation of the FcγR after IgG binding (reviewed in [1,2]). Upon activation, mast cells release either preformed, granule-stored mediators, such as histamine and proteases, or newly generated mediators, such as eicosanoids, cytokines, and chemokines [3]. Although the basic molecular mechanisms of Ig:Fc activation have been extensively studied in the past 15 years [4][5][6], new molecules regulating the Correspondence: Dr. Barbara Frossi e-mail: barbara.frossi@uniud.it FcR-signaling cascades have recently been characterized, suggesting not only a still vivid interest in the field of mast cell activation and signaling, but also in identifying putative new therapeutic targets for intervention in mast cell dependent disorders. This review will focus on three aspects of mast cell activation/function. First, we give an essential but complete overview of the FcR-mediated activation in mast cells and report on recent advances in IgE-and IgG-mediated signaling. For clarity, we will dissect and analyze the signals derived from each pathway, with particular attention to the newly identified positive or negative molecular players describing -when possible -their implication toward degranulation and cytokine production. Second, we highlight the growing interest aroun...

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Section: Lyn-sykmentioning

confidence: 99%

Mast cell activation: A complex interplay of positive and negative signaling pathways

Sibilano¹,

2014

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“…Recently, a number of studies have reported that stimulation of mast cells through FcεRI causes the production of intracellular reactive oxygen species (ROS); such compounds have been shown to act as second messengers in the signal transduction pathway leading to cytokine synthesis (7)(8)(9). However, neither the source of ROS generated in response to Ag stimulation nor the pathway by which they are generated in Ag-stimulated mast cells is clearly understood.…”

mentioning

confidence: 97%

BLT2 Is Upregulated in Allergen-Stimulated Mast Cells and Mediates the Synthesis of Th2 Cytokines

Cho

Seo

Lee

et al. 2010

The Journal of Immunology

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Mast cells are effector cells that mediate the allergic response through Ag stimulation of IgE bound to FcεRI. In allergic reactions, cross-linking of the surface receptors for IgE on mast cells results in the synthesis of Th2 cytokines such as IL-4 and IL-13, which are critical for the initiation and progression of the allergic response. Despite the important roles of these cytokines, the signaling mechanism by which Ag stimulation mediates the production of IL-4 and IL-13 in mast cells is not clearly understood. In the present study, we found that Ag-stimulated bone marrow-derived mast cells (BMMCs) highly upregulated the expression of BLT2, a leukotriene B4 receptor, and that blockade of BLT2 with the specific antagonist LY255283 or small interfering RNA knockdown completely abolished the production of Th2 cytokines. Furthermore, BMMCs overexpressing BLT2 showed significantly enhanced production of Th2 cytokines compared with wild-type BMMCs. Additionally, we found that the generation of Nox1-derived reactive oxygen species occurs downstream of BLT2, thus mediating the synthesis of Th2 cytokines. Taken together, our results suggest that the BLT2-Nox1-reactive oxygen species cascade is a previously unsuspected mediatory signaling mechanism to Th2 cytokine production in Ag-stimulated BMMCs, thus contributing to allergic response.

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“…The activation of MC and subsequent degranulation is calcium-dependent and results in elevated ROS levels [25]. It was hypothesized that FD reduced MC degranulation by blocking ROS production and calcium responses.…”

Section: The Effect Of Fd On Non-ige Mediated Induced Ros Activity Anmentioning

confidence: 99%

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

Dellinger¹,

Brooks

Plunkett

et al. 2012

J Nanomedic Nanotechnol

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Mast cells (MC) and peripheral blood basophils (PBB) are well known for their role in the allergic response mediated through high affinity IgE receptors (FcεRI). However, these cells can also be stimulated by other non-allergic secretagogues to release their inflammatory mediators. Certain fullerene derivatives (FD) have already been shown to stabilize FcεRI-mediated MC/PBB responses, but it is not know if they also stabilize these cells through non-IgEmediated mechanisms. A panel of FD was synthesized and tested for their ability to inhibit non-FcεRI mediated release from human MC and PBB. It was found that specifically engineered FD could significantly inhibit calcium ionophore, compound 48/80, somatostatin, and poly L-lysine induced MC degranulation and cytokine production, as well as blunt degranulation and cytokine production from N-formyl-methionine-leucine-phenylalanine (fMLP), poly L-lysine, and calcium ionophore stimulated PBB. The mechanism of inhibition was due in part to the prevention of secretagogueinduced increases in cellular reactive oxygen species (ROS) and calcium levels as well as the reduced activation of the MAPK signaling intermediates ERK1/ERK2 and LAT. Additionally, preincubation of MC with FD blunted the prostaglandin D 2 (PGD 2 ) production upon exposure to inflammatory stimuli. In both cell types, the extent of inhibition of mediator release in response to each secretagogue was dependent on the moieties/side chains attached to the carbon cage. These results further extend the utility of fullerene nanomaterials to control mediator release through non-IgE mediated pathways in MC/PBB.

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The role of reactive oxygen species and nitric oxide in mast cell‐dependent inflammatory processes

Cited by 189 publications

References 157 publications

Mast cell activation: A complex interplay of positive and negative signaling pathways

Mast cell activation: A complex interplay of positive and negative signaling pathways

BLT2 Is Upregulated in Allergen-Stimulated Mast Cells and Mediates the Synthesis of Th2 Cytokines

Effects of Novel Nanomaterials on Allergic Mediator Release from Human Mast Cells and Basophils through Non-Ige Mediated Pathways

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