FcεR1 and Toll-Like Receptors Mediate Synergistic Signals to Markedly Augment Production of Inflammatory Cytokines in Murine Mast Cells

Qiao, Haifa; Beaven, Michael A.

doi:10.1016/j.jaci.2005.12.1253

Cited by 72 publications

(131 citation statements)

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“…It is however unclear, whether degranulation itself can be induced via TLR directly. Some reports showed that TLR2 ligands are able to induce degranulation directly (38,39), but a clear mechanism cannot be defined yet, because such responses have not been observed consistently in all studies (40,41). At this point it should be noted that MCs exhibit some variation in phenotype according to anatomical location, species and culture conditions.…”

Section: Discussionmentioning

confidence: 96%

CCL17 Controls Mast Cells for the Defense against Filarial Larval Entry

Specht

Frank

Alferink

et al. 2011

The Journal of Immunology

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Filarial parasites have to trespass many barriers to successfully settle within their mammalian host, which is equipped with mechanical borders and complex weaponry of an evolved immune system. However, little is known about mechanisms of early local events in filarial infections. In this study, bone marrow-derived dendritic cells not only upregulated activation markers CD40 and CD80 upon in vitro stimulation with filarial extracts, but also secreted CCL17, a chemokine known to be produced upon microbial challenge. Mice deficient for CCL17 had an up to 4-fold higher worm burden compared with controls by day 10 of infection with the murine filaria Litomosoides sigmodontis. Also, numbers of mast cells (MCs) invading the skin and degranulation were significantly increased, which was associated with enhanced vascular permeability and larval establishment. This phenotype was reverted by inhibition of MC degranulation with disodium cromoglycate or by blockade of histamine. In addition, we showed that CCL17-mediated vascular permeability was dependent on the presence of Wolbachia endosymbionts and TLR2. Our findings reveal that CCL17 controls filarial larval entry by limiting MC-dependent vascular permeability.

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Section: Discussionmentioning

confidence: 96%

CCL17 Controls Mast Cells for the Defense against Filarial Larval Entry

Specht

Frank

Alferink

et al. 2011

The Journal of Immunology

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“…This concept is especially intriguing, because substances from bacteria, fungi, or viruses generally known as 'pathogen-associated molecular patterns' (PAMP) can directly bind to pathogen recognition receptors (PRR) leading to cell activation and immune modulation without the need of previous sensitization (66,67). It is well established that mast cells and basophils express PRR and are activated by different PAMP (68,69), which could alter their responsiveness (70). Indeed, it was shown that the PAMP peptidoglycan (PGN) can induce degranulation in human (71) and murine mast cells (72).…”

Section: Infections As Cofactors Of Anaphylaxismentioning

confidence: 99%

About the role and underlying mechanisms of cofactors in anaphylaxis

Wölbing

Fischer

Köberle

et al. 2013

Allergy

178

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Anaphylaxis is the systemic and most severe presentation of type I allergy. A number of conditions were identified that modulate the onset of anaphylaxis such as co-or augmentation factors, which significantly lower the allergen dose necessary for triggering anaphylaxis. Next to physical exercise or alcohol consumption, co-administration of nonsteroidal anti-inflammatory drugs (NSAID) or concomitant infectious diseases are well-documented cofactors of anaphylaxis. Registries for anaphylaxis document a role for cofactors in about 30% of anaphylactic reactions. Some disease entities such as 'wheat-dependent exercise-induced anaphylaxis' (WDEIA) are explicitly characterized by elicitation of anaphylaxis only in the presence of at least one such cofactor. Using WDEIA as a model disease, studies demonstrated that exercise increases skin prick test reactivity to and bioavailability of the allergen. Additional data indicate that alcohol consumption and NSAID administration display similar effects. Modulation of the cellular activation threshold is another mechanism underlying cofactor-induced anaphylaxis, most likely also functional when infectious diseases orchestrate elicitation of anaphylaxis. Cofactors are increasingly accepted to play a fundamental role in eliciting anaphylaxis. Consequently, to improve patient management modalities, a better understanding of the underlying mechanisms is warranted. This review aims to update clinicians and clinical scientists on recent developments.

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“…As an additional control, we measured TNF release triggered by stimulation with lipopolysaccharide, which occurs by a calciumindependent pathway 30,31 ; lipopolysaccharide-induced release of TNF was not different for Trpm4 +/+ and Trpm4 -/-BMMCs (Supplementary Fig. 8).…”

Section: Membrane Potential In Stimulated Bmmcsmentioning

confidence: 99%

Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4

et al. 2007

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Mast cells are key effector cells in allergic reactions. Aggregation of the receptor FceRI in mast cells triggers the influx of calcium (Ca 2+ ) and the release of inflammatory mediators. Here we show that transient receptor potential TRPM4 proteins acted as calcium-activated nonselective cation channels and critically determined the driving force for Ca 2+ influx in mast cells. Trpm4 -/-bone marrow-derived mast cells had more Ca 2+ entry than did TRPM4 +/+ cells after FceRI stimulation. Consequently, Trpm4 -/-bone marrow-derived mast cells had augmented degranulation and released more histamine, leukotrienes and tumor necrosis factor. Trpm4 -/-mice had a more severe IgE-mediated acute passive cutaneous anaphylactic response, whereas late-phase passive cutaneous anaphylaxis was not affected. Our results establish the physiological function of TRPM4 channels as critical regulators of Ca 2+ entry in mast cells.Mast cells are bone marrow-derived hematopoietic cells localized near surfaces exposed to the environment, such as the skin, the airway epithelia and the intestine, where pathogens, allergens and other environmental agents are frequently encountered 1 . Activation and degranulation of mast cells is a key step in the pathogenesis of allergic diseases such as bronchial asthma and systemic anaphylaxis 2 . An allergic reaction develops when allergens encountered by antigen-presenting cells are processed and presented to T cells. Ensuing T helper type 2 responses cause B cells to produce allergen-specific immunoglobulin E (IgE). The IgE molecules bind to the receptor FceRI on the surfaces of mast cells. After re-exposure to the allergen, FceRI-associated IgE molecules bind allergen and aggregate, thereby activating mast cells. Activated mast cells secrete preformed mediators, including proteases and vasoactive amines, such as histamine, that are stored in cytoplasmic granules. In addition, mast cell activation results in the de novo synthesis of proinflammatory lipid mediators, cytokines and chemokines. The instant release of histamine is crucial for the development of immediate-type allergic reactions that result in vasodilatation, increased vascular permeability and smooth muscle contraction 1,2 . In addition, IgE-dependent mast cell activation may be complemented by signaling cascades triggered by several endogenous ligands, such as adenosine, resulting in the amplification and maintenance of FceRI-mediated degranulation 3,4 .FceRI crosslinking activates many signaling molecules 5,6 . A chief 'downstream' target is phospholipase C-g1, which catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to diacylglycerol and inositol-1,4,5-trisphosphate 5 . In contrast, adenosine stimulation involves the activation of G ai protein-coupled A 3 adenosine receptors in mouse mast cells, which leads to the activation of phospholipase C and phospholipase D through G bg protein and phosphatidylinositol-3-OH kinase-g 7,8 . Inositol-1,4,5-trisphosphate and diacylglycerol promote the activation of protein kinase C an...

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FcεR1 and Toll-Like Receptors Mediate Synergistic Signals to Markedly Augment Production of Inflammatory Cytokines in Murine Mast Cells

Cited by 72 publications

References 0 publications

CCL17 Controls Mast Cells for the Defense against Filarial Larval Entry

CCL17 Controls Mast Cells for the Defense against Filarial Larval Entry

About the role and underlying mechanisms of cofactors in anaphylaxis

Increased IgE-dependent mast cell activation and anaphylactic responses in mice lacking the calcium-activated nonselective cation channel TRPM4

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