Interacting mast cells and eosinophils acquire an enhanced activation state <i>in vitro</i>

Elishmereni, Moran; Bachelet, Ido; Ben-Efraim, A. H. Nissim; Mankuta, David; Levi‐Schaffer, Francesca

doi:10.1111/all.12059

Cited by 64 publications

(52 citation statements)

References 63 publications

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“…In the context of the newly developed concept of physical interaction between both cells types, leading to mutual enhancement of their respective functional responses (Elishmereni et al, 2011(Elishmereni et al, , 2013, the ability of CEE-1 Fig. 8.…”

Section: Novel Enhydrazinone Ester Effective In Allergy and Asthmamentioning

confidence: 99%

“…Recently, an interesting concept of physical interaction between both cells types leading to mutual enhancement of their respective functional responses, the socalled "Allergic Effector Unit," has been developed (Elishmereni et al, 2011(Elishmereni et al, , 2013. Such interplay may be critical in sustaining chronic allergic inflammation, such as in asthma, where it may be particularly relevant in the "eosinophilic" endotype of the disease.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, drugs that are able to directly affect both cell types simultaneously would be expected to have potential advantages. This is particularly so given the idea that the recently described physical interplay between the two cell types may be the critical factor driving chronic allergic inflammation (Elishmereni et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Antiallergic and Antiasthmatic Effects of a Novel Enhydrazinone Ester (CEE-1): Inhibition of Activation of Both Mast Cells and Eosinophils

Ezeamuzie

El-Hashim

Renno

et al. 2014

J Pharmacol Exp Ther

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Activation of mast cells and eosinophils is a fundamental process in the pathophysiology of allergic diseases. We have previously reported that the novel enhydrazinone ester CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate) possesses potent anti-inflammatory activity. We have now tested whether the compound also possesses antiallergic and antiasthmatic effects in vitro and in vivo. The compound significantly inhibited degranulation and leukotriene C 4 (LTC 4 ) release from activated human eosinophils, as well as IgE-dependent degranulation and LTC 4 release from passively sensitized rat basophilic leukemia cells and bone marrow-derived mouse mast cells. In human eosinophils, the drug was more potent in inhibiting degranulation than LTC 4 release {IC 50 5 0.4 mM [confidence interval (CI): 0.1-0.9] versus 3.8 mM (CI: 0.9-8.3)}, whereas in mast cells the reverse was essentially the case. The drug did not affect stimulus-induced calcium transients in eosinophils but significantly inhibited early phosphorylation of extracellular signal-regulated kinases 1/2 and p38-mitogen-activated protein kinases (MAPK). In vivo, topical application of 4.5-15 mg/kg of the compound significantly inhibited allergen-induced passive cutaneous anaphylaxis in mice. Similarly, in the mouse asthma model, the intranasal administration of 6.5-12.5 mg/kg of the compound significantly inhibited bronchial inflammation and eosinophil accumulation in bronchial lavage fluid, as well as abolishing airway hyperresponsiveness to methacholine. These results show that CEE-1 inhibits the activation of both mast cells and eosinophils in vitro, probably by blocking MAPK-activation pathways, and that these effects are translated into antiallergic and antiasthmatic effects in vivo. The compound, therefore, has potential application in the treatment of asthma and other allergic diseases.

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Section: Novel Enhydrazinone Ester Effective In Allergy and Asthmamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antiallergic and Antiasthmatic Effects of a Novel Enhydrazinone Ester (CEE-1): Inhibition of Activation of Both Mast Cells and Eosinophils

Ezeamuzie

El-Hashim

Renno

et al. 2014

J Pharmacol Exp Ther

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“…19 The late/chronic phase is mainly attributed to the effects of infiltrating eosinophils and their derivatives. 20 Exosomes released from both immune and structural cells in the lung 21,22 have recently been shown to play an important role in local regulation of asthma pathology. 23 Moreover, exosomes from asthmatic patients differ in quantity, composition, and function compared with those from healthy subjects, 24 which demonstrates the implication of exosomes in regulation of asthma pathology.…”

mentioning

confidence: 99%

Exosome secretion by eosinophils: A possible role in asthma pathogenesis

Mazzeo

Cañas

Zafra

et al. 2015

Journal of Allergy and Clinical Immunology

106

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“…6, 7); soluble ligands, most of which bind to G-protein-coupled receptors (reviewed in Ref. 8); and cell-cell contact (9)(10)(11)(12). A signaling cascade is then initiated that culminates in cell degranulation (13).…”

mentioning

confidence: 99%

Rab12 Regulates Retrograde Transport of Mast Cell Secretory Granules by Interacting with the RILP–Dynein Complex

Efergan

Azouz

Klein

et al. 2016

The Journal of Immunology

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Secretory granule (SG) transport is a critical step in regulated exocytosis including degranulation of activated mast cells. The latter process results in the release of multiple inflammatory mediators that play key roles in innate immunity, as well as in allergic responses. In this study, we identified the small GTPase Rab12 as a novel regulator of mast cell SG transport, and we provide mechanistic insights into its mode of action. We show that Rab12 is activated in a stimulus-dependent fashion and promotes microtubule-dependent retrograde transport of the SGs in the activated cells. We also show that this minus end transport of the SGs is mediated by the RILP–dynein complex and identify RILP as a novel effector of Rab12. Finally, we show that Rab12 negatively regulates mast cell degranulation. Taken together, our results identify Rab12 as a novel regulator of mast cell responses and disclose for the first time, to our knowledge, the mechanism of retrograde transport of the mast cell SGs.

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Interacting mast cells and eosinophils acquire an enhanced activation state in vitro

Cited by 64 publications

References 63 publications

Antiallergic and Antiasthmatic Effects of a Novel Enhydrazinone Ester (CEE-1): Inhibition of Activation of Both Mast Cells and Eosinophils

Antiallergic and Antiasthmatic Effects of a Novel Enhydrazinone Ester (CEE-1): Inhibition of Activation of Both Mast Cells and Eosinophils

Exosome secretion by eosinophils: A possible role in asthma pathogenesis

Rab12 Regulates Retrograde Transport of Mast Cell Secretory Granules by Interacting with the RILP–Dynein Complex

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