Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro

Elishmereni, Moran; Alenius, Harri; Bradding, Peter; Mizrahi, Sa’ar; Shikotra, Aarti; Minai-Fleminger, Yael; Mankuta, David; Eliashar, Ron; Zabucchi, Giuliano; Levi‐Schaffer, Francesca

doi:10.1111/j.1398-9995.2010.02494.x

Cited by 87 publications

(73 citation statements)

References 34 publications

(60 reference statements)

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“…It was proved that both the populations can mutually affect their biological activity through released cytokines and a direct cell-to-cell (ligand-receptor) contact. This interaction is strong and protects eosinophils against dexametazone-induced apoptosis [30]. Thus, the modulation of the number of both cellular populations, their functions and mutual interactions in the inflammatory infiltrate seems to be highly important in the control of chronic inflammation associated with asthma.…”

Section: Pharmacodynamic Properties Of Omalizumabmentioning

confidence: 99%

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

Kupryś‐Lipińska¹,

Molińska²,

Kuna³

2016

Advances in Respiratory Medicine

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Bronchial asthma is characterised by high levels of immunoglobulin E (IgE) and overproduction of pro-inflammatory cytokines, including interleukins IL-4, IL-13 and IL-5 needed for, amongst other things, the production of IgE and the differentiation, maturation, migration and survival of eosinophils. Eosinophils are one of the most important cells in allergic inflammation. Their presence in tissue is linked to the persistence of inflammatory infiltrate, tissue damage and remodelling. Although these cells are very sensitive to corticosteroids, some asthmatic patients do not respond to high doses of these drugs, even when administered systemically. Transbronchial biopsies and bronchoalveolar lavage performed in patients with steroid-resistant asthma have demonstrated higher levels of eosinophils and Th2-type cytokines (IL-4 and IL-5) compared to steroid-sensitive patients. Clinical studies have confirmed that the very effective treatment in these cases is therapy with omalizumab -an anti-IgE monoclonal antibody. The paper discusses the efficacy of omalizumab in reducing eosinophil number in peripheral blood and in the airways of asthmatic patients based on basic, clinical, observational studies and case reports. The significance of omalizumab therapy in asthma control and mechanisms that regulate the effects of omalizumab on eosinophils are evaluated.

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Section: Pharmacodynamic Properties Of Omalizumabmentioning

confidence: 99%

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

Kupryś‐Lipińska¹,

Molińska²,

Kuna³

2016

Advances in Respiratory Medicine

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“…Human peripheral blood was collected from healthy donors in accordance with a protocol that was approved by the institutional ethics committee. Neutrophils were isolated using Histopaque Percoll (Sigma) as described before (49) or by negative selection (50) and brought to a concentration of 1 ϫ 10 7 cells/ml in Hanks buffer (Biological Industries, Kibbutz Beit Haemek, Israel). Neutrophil purity was determined by flow cytometry using antibodies to CD66b and CD16 (BioLegend, USA).…”

Section: Methodsmentioning

confidence: 99%

LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

et al. 2013

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Host defense peptides are immediate responders of the innate immunity that express antimicrobial, immunoregulatory, and wound-healing activities. Neutrophils are a major source for oral host defense peptides, and phagocytosis by neutrophils is a major mechanism for bacterial clearance in the gingival tissue. Dysfunction of or reduction in the numbers of neutrophils or deficiency in the LL-37 host defense peptide was each previously linked with proliferation of oral Aggregatibacter actinomycetemcomitans which resulted in an aggressive periodontal disease. Surprisingly, A. actinomycetemcomitans shows resistance to high concentrations of LL-37. In this study, we demonstrated that submicrocidal concentrations of LL-37 inhibit biofilm formation by A. actinomycetemcomitans and act as opsonins and agglutinins that greatly enhance its clearance by neutrophils and macrophages. Improved uptake of A. actinomycetemcomitans by neutrophils was mediated by their opsonization with LL-37. Enhanced phagocytosis and killing of A. actinomycetemcomitans by murine macrophage-like RAW 264.7 cells were dependent on their preagglutination by LL-37. Although A. actinomycetemcomitans is resistant to the bactericidal effect of LL-37, our results offer a rationale for the epidemiological association between LL-37 deficiency and the expansion of oral A. actinomycetemcomitans and indicate a possible therapeutic use of cationic peptides for host defense.

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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%

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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Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro

Abstract: Our findings provide the first evidence for a complex network of paracrine and membrane interactions between MCs and Eos. The prosurvival phenotype induced by this MC-Eos interplay may be critical for sustaining chronic allergic inflammation.

Cited by 87 publications

References 34 publications

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

The Effect of Omalizumab on Eosinophilic Inflammation of the Respiratory Tract in Patients with Allergic Asthma

LL-37 Opsonizes and Inhibits Biofilm Formation of Aggregatibacter actinomycetemcomitans at Subbactericidal Concentrations

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

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