Eosinophils Induce Airway Smooth Muscle Cell Proliferation

Halwani, Rabih; Vazquez-Tello, Alejandro; Sumi, Yuki; Pureza, Mary Angeline; BaHammam, Ahmed S.; Al-Jahdali, Hamdan; Gounni, Abdelilah Soussi; Mahboub, Bassam; Al‐Muhsen, Saleh; Hamid, Qutayba

doi:10.1007/s10875-012-9836-3

Cited by 42 publications

(39 citation statements)

References 51 publications

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“…Halwani et al (2013) verified that preventing eosinophil contact with ASM cells using specific antibodies or blocking cysteinyl leukotrienes derived from eosinophils was associated with inhibition of ASM proliferation. Moreover, ASM-synthesized cytokines seem to direct the eosinophil differentiation and maturation from progenitor cells, which can promote perpetuation of eosinophilic inflammation and consequently the tissue remodeling in asthma (Fanat et al, 2009).…”

Section: Airway Smooth Musclementioning

confidence: 71%

Pathology of asthma

Kudo¹,

Ishigatsubo²,

Aoki³

2013

Front. Microbiol.

299

213

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Asthma is a serious health and socioeconomic issue all over the world, affecting more than 300 million individuals. The disease is considered as an inflammatory disease in the airway, leading to airway hyperresponsiveness, obstruction, mucus hyper-production and airway wall remodeling. The presence of airway inflammation in asthmatic patients has been found in the nineteenth century. As the information in patients with asthma increase, paradigm change in immunology and molecular biology have resulted in an extensive evaluation of inflammatory cells and mediators involved in the pathophysiology of asthma. Moreover, it is recognized that airway remodeling into detail, characterized by thickening of the airway wall, can be profound consequences on the mechanics of airway narrowing and contribute to the chronic progression of the disease. Epithelial to mesenchymal transition plays an important role in airway remodeling. These epithelial and mesenchymal cells cause persistence of the inflammatory infiltration and induce histological changes in the airway wall, increasing thickness of the basement membrane, collagen deposition and smooth muscle hypertrophy and hyperplasia. Resulting of airway inflammation, airway remodeling leads to the airway wall thickening and induces increased airway smooth muscle mass, which generate asthmatic symptoms. Asthma is classically recognized as the typical Th2 disease, with increased IgE levels and eosinophilic inflammation in the airway. Emerging Th2 cytokines modulates the airway inflammation, which induces airway remodeling. Biological agents, which have specific molecular targets for these Th2 cytokines, are available and clinical trials for asthma are ongoing. However, the relatively simple paradigm has been doubted because of the realization that strategies designed to suppress Th2 function are not effective enough for all patients in the clinical trials. In the future, it is required to understand more details for phenotypes of asthma.

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Section: Airway Smooth Musclementioning

confidence: 71%

Pathology of asthma

Kudo¹,

Ishigatsubo²,

Aoki³

2013

Front. Microbiol.

299

213

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“…Our results demonstrate ECM protein production by ASM cells after exposure to eosinophils from asthma and control groups in vitro . However, Halwani et al (2013) suggested that ASM cells proliferation increase irrespective of ECM proteins production in asthma and presume that eosinophils enhance ASM proliferation via the release of CysLTs.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma

et al. 2017

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Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact through integrin–ligand interactions. Eosinophils express several types of outer membrane integrin, which are responsible for cell–cell and cell–extracellular matrix interactions. In our previous study we demonstrated that asthmatic eosinophils show increased adhesion to ASM cells and it may be important factor contributing to ASM remodeling in asthma. According to these findings, in the present study we investigated the effects of suppression of eosinophil integrin on eosinophil-induced ASM remodeling in asthma.Materials and Methods: Individual combined cell cultures of immortalized human ASM cells and eosinophils from peripheral blood of 22 asthmatic patients and 17 healthy controls were prepared. Eosinophil adhesion was evaluated using eosinophil peroxidase activity assay. Genes expression levels in ASM cells and eosinophils were measured using quantitative real-time PCR. ASM cell proliferation was measured using alamarBlue® solution. Eosinophil integrins were blocked by incubating with Arg-Gly-Asp-Ser peptide.Results: Eosinophils from the asthma group showed increased outer membrane α4β1 and αMβ2 integrin expression, increased adhesion to ASM cells, and overexpression of TGF-β1 compared with eosinophils from the healthy control group. Blockade of eosinophil RGD-binding integrins by Arg-Gly-Asp-Ser peptide significantly reduced adhesion of eosinophils to ASM cells in both groups. Integrin-blocking decreased the effects of eosinophils on TGF-β1, WNT-5a, and extracellular matrix protein gene expression in ASM cells and ASM cell proliferation in both groups. These effects were more pronounced in the asthma group compared with the control group.Conclusion: Suppression of eosinophil-ASM interaction via RGD-binding integrins attenuates eosinophil-induced ASM remodeling in asthma.Trial Registration: ClinicalTrials.gov Identifier: NCT02648074.

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“…Eosinophils isolated from asthmatics, when cocultured with ASM cells, promote enhanced ASM proliferation, which is inhibited by the addition of the leukotriene antagonist montelukast (117). It appears that eosinophils and ASM enjoy a reciprocal relationship, as ASM cells are also known to produce pro-eosinophil cytokines (118).…”

Section: The Eosinophil’s Role In Asthma Pathophysiologymentioning

confidence: 99%

The Biology of Eosinophils and Their Role in Asthma

2017

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This review will describe the structure and function of the eosinophil. The roles of several relevant cell surface molecules and receptors will be discussed. We will also explore the systemic and local processes triggering eosinophil differentiation, maturation, and migration to the lungs in asthma, as well as the cytokine-mediated pathways that result in eosinophil activation and degranulation, i.e., the release of multiple pro-inflammatory substances from eosinophil-specific granules, including cationic proteins, cytokines, chemokines growth factors, and enzymes. We will discuss the current understanding of the roles that eosinophils play in key asthma processes such as airway hyperresponsiveness, mucus hypersecretion, and airway remodeling, in addition to the evidence relating to eosinophil–pathogen interactions within the lungs.

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Eosinophils Induce Airway Smooth Muscle Cell Proliferation

Cited by 42 publications

References 51 publications

Pathology of asthma

Pathology of asthma

Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma

The Biology of Eosinophils and Their Role in Asthma

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