Mechanisms of mast cell signaling in anaphylaxis

Metcalfe, Dean D.; Peavy, Richard D.; Gilfillan, Alasdair M.

doi:10.1016/j.jaci.2009.08.035

Cited by 256 publications

(276 citation statements)

References 70 publications

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“…The release of histamine and other pharmacological mediator from mast cells is a prominent feature of acute inflammatory processes including the immediate type anaphylactic reactions. There are various agents to induce the mast cell degranulation, which are commonly associated with the anaphylactic shocks in human and other mammals (Jippo et al, 2009;Metcalfe et al, 2009;Ono et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Activity of Constituents Isolated from Ulmus davidiana var. japonica

Zheng¹,

Yang²,

Li³

et al. 2010

Biomolecules and Therapeutics

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-Twenty six compounds (1-26) were isolated from the root barks of Ulmus davidiana var. japonica. The anti-inflammatory activity of the isolated compounds were evaluated against the generation of inflammatory chemical mediators in bone marrow-derived mast cells. Among them, compounds 10, 11, 13, 15 and 19 inhibited not only cyclooxygenase-2 dependent prostaglandin D2 generation but also 5-lipoxygenase dependent leukotrien C 4 generation in a concentration-dependent manner. In addition, compounds 11, 12, 13, 15 and 19 also inhibited β-hexosaminidase release, a marker of mast cell degranulation reaction, from bone marrow-derived mast cell. These results suggest that the anti-inflammatory activity of U. davidiana might in part occur by both the inhibition of eicosanoid generations and the degranulation reaction of mast cells.

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Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Activity of Constituents Isolated from Ulmus davidiana var. japonica

Zheng¹,

Yang²,

Li³

et al. 2010

Biomolecules and Therapeutics

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“…Ag receptor stimulation in T and B lymphocytes and mast cells culminates in NF-kB activation (3,4). The activity of NF-kB signaling pathway is tightly controlled by the inhibitory kB kinase (IKK) complex, which consists of IKKa, IKKb, and IKKg (also known as NF-kB essential modifier), together with its downstream substrate IkBa.…”

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confidence: 99%

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Goh

Cook

Upton

et al. 2013

The Journal of Immunology

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Persistent activation of NF-κB has been associated with the development of asthma. Receptor-interacting protein 2 (Rip2) is a transcriptional product of NF-κB activation. It is an adaptor protein with serine/threonine kinase activity and has been shown to positively regulate NF-κB activity. We investigated potential protective effects of Rip2 gene silencing using small interfering RNA (siRNA) in an OVA-induced mouse asthma model. Rip2 protein level was found to be upregulated in allergic airway inflammation. A potent and selective Rip2 siRNA given intratracheally knocked down Rip2 expression in OVA-challenged lungs and reduced OVA-induced increases in total and eosinophil counts, and IL-4, IL-5, IL-13, IL-1β, IL-33, and eotaxin levels in bronchoalveolar lavage fluid. Rip2 silencing blocked OVA-induced inflammatory cell infiltration and mucus hypersecretion as observed in lung sections, and mRNA expression of ICAM-1, VCAM-1, E-selectin, RANTES, IL-17, IL-33, thymic stromal lymphopoietin, inducible NO synthase, and MUC5ac in lung tissues. In addition, elevation of serum OVA-specific IgE level in mouse asthma model was markedly suppressed by Rip2 siRNA, together with reduced IL-4, IL-5, and IL-13 production in lymph node cultures. Furthermore, Rip2 siRNA-treated mice produced significantly less airway hyperresponsiveness induced by methacholine. Mechanistically, Rip2 siRNA was found to enhance cytosolic level of IκBα and block p65 nuclear translocation and DNA-binding activity in lung tissues from OVA-challenged mice. Taken together, our findings clearly show that knockdown of Rip2 by gene silencing ameliorates experimental allergic airway inflammation, probably via interruption of NF-κB activity, confirming Rip2 a novel therapeutic target for the treatment of allergic asthma.

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“…Historically, clinical symptoms arising from MCA have mostly been studied in the context of allergies or atopic disorders (18)(19)(20). More recently, however, MCA has also been Allergy 68 (2013) 417-424…”

Section: Introductionmentioning

confidence: 99%

“…Severe or even life-threatening MCA may occur when the burden of mast cells is high and/or these cells are in an hyperactivated state. In these cases, a MCA syndrome (MCAS) may be diagnosed.Historically, clinical symptoms arising from MCA have mostly been studied in the context of allergies or atopic disorders (18)(19)(20). More recently, however, MCA has also been Allergy 68 (2013) 417-424…”

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confidence: 99%

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Mast cell activation syndromes: definition and classification

Valent

2013

Allergy

104

165

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Mast cell activation (MCA) occurs in a number of different clinical conditions, including IgE-dependent allergies, other inflammatory reactions, and mastocytosis. MCA-related symptoms may be mild, moderate, severe, or even life-threatening. The severity of MCA depends on a number of different factors, including genetic predisposition, the number and releasability of mast cells involved in the reaction, the type of allergen, presence of specific IgE, and presence of certain comorbidities. In severe reactions, MCA can be documented by a substantial increase in the serum tryptase level above baseline. When symptoms are recurrent, are accompanied by an increase in mast cell-derived mediators in biological fluids, and are responsive to treatment with mast cell-stabilizing or mediator-targeting drugs, the diagnosis of mast cell activation syndrome (MCAS) is appropriate. Based on the underlying condition, these patients can further be classified into i) primary MCAS where KIT-mutated, clonal mast cells are detected, ii) secondary MCAS where an underlying inflammatory disease, often in the form of an IgE-dependent allergy, but no KIT-mutated mast cells, is found, and iii) idiopathic MCAS, where neither an allergy or other underlying disease, nor KITmutated mast cells are detectable. It is important to note that in many patients with MCAS, several different factors act together to lead to severe or even lifethreatening anaphylaxis. Detailed knowledge about the pathogenesis and complexity of MCAS, and thus establishing the exact final diagnosis, may greatly help in the management and therapy of these patients.Mast cells are tissue-fixed effector cells of allergic and other inflammatory reactions (1-5). In common with blood basophils, mast cells express high-affinity IgE-binding sites and store numerous proinflammatory and vasoactive mediators in their metachromatic granules (1-3). During a severe anaphylactic reaction, allergen-induced cross-linking of IgE-binding sites on mast cells is followed by an explosive release of granular mediators (1-3, 5-7). In addition, activated mast cells release newly synthesized membrane-derived (lipid) mediators of allergic reactions into the extracellular space. Blood basophils also participate in allergic and other inflammatory reactions in the same way as mast cells (1,8,9). However, not all allergic reactions involve both cell types, even if the reaction is systemic. In addition, some of the mediators relevant to anaphylactic reactions are produced and released primarily in mast cells but not in basophils, or only in blood basophils but not in tissue mast cells.The capacity of mast cells and basophils to release mediators of anaphylaxis in response to cell activation, also termed 'releasability', depends on a number of different factors, including the primary underlying disease, number and type of (pre)activated receptors and signaling cascades, and the genetic background (9-13). The severity of an anaphylactic reaction is determined by additional factors, including the number...

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Mechanisms of mast cell signaling in anaphylaxis

Cited by 256 publications

References 70 publications

Anti-Inflammatory Activity of Constituents Isolated from Ulmus davidiana var. japonica

Anti-Inflammatory Activity of Constituents Isolated from Ulmus davidiana var. japonica

Receptor-Interacting Protein 2 Gene Silencing Attenuates Allergic Airway Inflammation

Mast cell activation syndromes: definition and classification

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