The Enhanced Adhesion of Eosinophils Is Associated with Their Prolonged Viability and Pro-Proliferative Effect in Asthma

Januškevičius, Andrius; Janulaitytė, Ieva; Kalinauskaitė-Žukauskė, Virginija; Gosens, Reinoud; Malakauskas, Kęstutis

doi:10.3390/jcm8091274

Cited by 10 publications

(20 citation statements)

References 52 publications

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“…Eosinophils' survivability-promoting factors are mainly associated with cytokines, released by type 2 T helper cells and type 2 innate lymphoid cells [13,14]. There is evidence that the direct interaction of eosinophils with pulmonary structural cells promotes their survivability [15][16][17], but the precise mechanisms remain unknown. The peribronchial area was usually considered as eosinophils localization in asthma [18].…”

Section: Introductionmentioning

confidence: 99%

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Blood Eosinophils Subtypes and Their Survivability in Asthma Patients

Januškevičius

Jurkevičiūtė

Janulaitytė

et al. 2020

Cells

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Eosinophils subtypes as lung-resident (rEOS) and inflammatory (iEOS) eosinophils are different in surface protein expression, functions, response to IL-5 and localization in lungs. rEOS- and iEOS-like eosinophils are found in blood; thus, we aimed to investigate their quantity and survivability in asthma patients. A total of 40 individuals were included: 10 steroid-free non-severe allergic asthma (AA), and 18 severe non-allergic eosinophilic asthma (SNEA) patients, the control group consisted of 12 healthy non-smoking subjects (HS). A bronchial challenge with Dermatophagoides pteronysinnus allergen was performed for AA patients and HS. Blood eosinophils subtyping was completed with magnetic beads’ conjugated antibodies against surface CD62L. Eosinophils adhesion to hTERT airway smooth muscle (ASM) cells was measured by evaluating their peroxidase activity and viability by annexin V and propidium iodide staining. We found that the predominant blood eosinophil subtype in AA patients was iEOS, while rEOS prevailed in SNEA patients (p < 0.05). Moreover, rEOS demonstrated higher adhesion intensity compared with iEOS in all investigated groups. Both eosinophils subtypes of SNEA patients had higher survivability over the AA group. However, iEOS survivability from AA and SNEA groups was higher compared with rEOS under standard conditions, when rEOS survivability increased after their incubation with ASM cells. Bronchial allergen challenge abolished the dominance of blood iEOS in AA patients and prolonged only iEOS survivability. Though the challenge did not affect the adhesion of any eosinophils subtypes, the direct dependence of rEOS and iEOS survivability on their interaction with ASM cells was revealed (p < 0.05). These findings provide the premise for eosinophils subtype-oriented asthma treatment.

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Section: Introductionmentioning

confidence: 99%

“…Due to different localization and behavior of eosinophils subtypes after migration to asthmatic lungs, rEOS and iEOS could vary in adhesion properties. Adhesion is essential for eosinophils infiltration into the airways and could be recognized as a survivability-promoting factor [15,19].…”

Section: Introductionmentioning

confidence: 99%

Blood Eosinophils Subtypes and Their Survivability in Asthma Patients

Januškevičius

Jurkevičiūtė

Janulaitytė

et al. 2020

Cells

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“…It shows that AA eosinophils are more activated as the molecules that are responsible for adherence are upregulated, and it helps eosinophils to migrate through the wall of vessels and continue the movement to bronchial tissue interacting with pulmonary structural cells and ECM proteins. Previously we showed that in vivo allergen-activated eosinophils demonstrate a higher adhesion, viability, and pro-proliferative effect on ASM cells and pulmonary fibroblasts compared to non-activated eosinophils [33]. A possible limitation of this study is that we used peripheral blood eosinophils instead of airway tissue eosinophils.…”

Section: Discussionmentioning

confidence: 97%

“…Cell-ECM and cell-cell interaction is generally controlled by integrins, and this interaction is required not only for eosinophils rolling and tethering but also for their activation [48]. We previously demonstrated that adhesion of eosinophils to pulmonary structural cells or ECM proteins increases their viability [33]. Eosinophils express seven integrins heterodimers, and each type interacts with its own set of ligands, which may be deposited in ECM or as a counter-receptor on other cells [31].…”

Section: Discussionmentioning

confidence: 99%

“…Eosinophils produce increased levels of MMP-9, ROS as well as TGF-β in asthma [59][60][61]. Prolonged viability of eosinophils after migration to airways and adhesion to ECM and/or ASM cells creates conditions for the secretion of mediators by eosinophils [33]. It was shown that ASM cells can activate TGF-β1 via αVβ5 integrins-specifically through the β5 cytoplasmic domain [62].…”

Section: Discussionmentioning

confidence: 99%

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In Vivo Allergen-Activated Eosinophils Promote Collagen I and Fibronectin Gene Expression in Airway Smooth Muscle Cells via TGF-β1 Signaling Pathway in Asthma

Janulaitytė

Januškevičius

Kalinauskaitė-Žukauskė

et al. 2020

IJMS

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Eosinophils infiltration and releasing TGF-β1 in the airways has been implicated in the pathogenesis of asthma, especially during acute episodes provoked by an allergen. TGF-β1 is a major mediator involved in pro-inflammatory responses and fibrotic tissue remodeling in asthma. We aimed to evaluate the effect of in vivo allergen-activated eosinophils on the expression of COL1A1 and FN in ASM cells in asthma. A total of 12 allergic asthma patients and 11 healthy subjects were examined. All study subjects underwent bronchial challenge with D. pteronyssinus allergen. Eosinophils from peripheral blood were isolated before and 24 h after the bronchial allergen challenge using high-density centrifugation and magnetic separation. Individual co-cultures of blood eosinophils and immortalized human ASM cells were prepared. The TGF-β1 concentration in culture supernatants was analyzed using ELISA. Gene expression was analyzed using qRT-PCR. Eosinophils integrins were suppressed with linear RGDS peptide before co-culture with ASM cells. Results: The expression of TGF-β1 in asthmatic eosinophils significantly increased over non-activated asthmatic eosinophils after allergen challenge, p < 0.001. The TGF-β1 concentration in culture supernatants was significantly higher in samples with allergen-activated asthmatic eosinophils compared to baseline, p < 0.05. The effect of allergen-activated asthmatic eosinophils on the expression of TGF-β1, COL1A1, and FN in ASM cells was more significant compared to non-activated eosinophils, p < 0.05, however, no difference was found on WNT-5A expression. The incubation of allergen-activated asthmatic eosinophils with RGDS peptide was more effective compared to non-activated eosinophils as the gene expression in ASM cells was downregulated equally to the same level as healthy eosinophils.

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Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis

Lü¹,

Zhou²,

Wang³

et al. 2023

JIR

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Bronchial asthma is a complex heterogeneous airway disease, which has emerged as a global health issue. A comprehensive understanding of the different molecular mechanisms of bronchial asthma may be an efficient means to improve its clinical efficacy in the future. Increasing research evidence indicates that some types of programmed cell death (PCD), including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, contributed to asthma pathogenesis, and may become new targets for future asthma treatment. This review briefly discusses the molecular mechanism and signaling pathway of these forms of PCD focuses on summarizing their roles in the pathogenesis and treatment strategies of asthma and offers some efficient means to improve clinical efficacy of therapeutics for asthma in the near future.

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The Enhanced Adhesion of Eosinophils Is Associated with Their Prolonged Viability and Pro-Proliferative Effect in Asthma

Cited by 10 publications

References 52 publications

Blood Eosinophils Subtypes and Their Survivability in Asthma Patients

Blood Eosinophils Subtypes and Their Survivability in Asthma Patients

In Vivo Allergen-Activated Eosinophils Promote Collagen I and Fibronectin Gene Expression in Airway Smooth Muscle Cells via TGF-β1 Signaling Pathway in Asthma

Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis

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