Tissue factor–bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo

Park, Jin Ah; Sharif, Asma; Tschumperlin, Daniel J.; Lau, Laurie; Limbrey, Rachel; Howarth, Peter H.; Drazen, Jeffrey M.

doi:10.1016/j.jaci.2012.05.031

Cited by 99 publications

(122 citation statements)

References 45 publications

(58 reference statements)

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“…We previously showed that compressive stress at 30 cm H 2 O increases TF mRNA expression in NHBE cells (21). Here, we examined if TF mRNA expression is dependent on the magnitude of pressure.…”

Section: Compressive Stress Increases Tf Mrna Expression In Nhbe Cellmentioning

confidence: 92%

“…We previously reported that TF expression is significantly higher in the airway epithelium and BAL fluid from subjects with asthma versus normal subjects (21). Here, we examined if the increase in TF expression in patients with asthma can be recapitulated in an allergic mouse model of asthma.…”

Section: Tf Is Elevated In the Bal Fluid Of Ova-challenged Micementioning

confidence: 94%

“…We previously showed that TF-positive extracellular vesicles are released into the basolateral CM from compressed NHBE cells in ALI culture (21). We measured the level of TF activity in the CM using a clotting assay (30).…”

Section: Compressive Stress Increases Tf Mrna Expression In Nhbe Cellmentioning

confidence: 99%

“…It is expressed in a variety of cell types, including airway epithelial cells (20). Previously, we showed that TF expression is increased in the airway epithelium of patients with asthma and that bronchial epithelial cells are a source of TF (21). In a mouse model of asthma, mice with a severe deficiency of FVII have attenuation of airway hyperresponsiveness and mucus production induced by allergen challenge (22).…”

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confidence: 99%

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IL-13 Augments Compressive Stress–Induced Tissue Factor Expression in Human Airway Epithelial Cells

Mitchel¹,

Antoniak

Kim

et al. 2016

Am J Respir Cell Mol Biol

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Tissue factor (TF) is best known as a cellular initiator of coagulation, but it is also a multifunctional protein that has been implicated in multiple pathophysiologic conditions, including asthma. In the lung, airway epithelial cells express TF, but it is unknown how TF expression is regulated by asthma-associated mediators. We investigated the role of IL-13, a type 2 cytokine, alone and in combination with compressive stress, which mimics asthmatic bronchoconstriction, on TF expression and release of TF-positive extracellular vesicles from primary normal human bronchial epithelial cells. Well-differentiated normal human bronchial epithelial cells were treated with IL-13 and compressive stress, alone and in combination. TF mRNA, protein and activity were measured in the cells and conditioned media. TF was also measured in the bronchoalveolar lavage (BAL) fluid of allergen-challenged mice and patients with asthma. IL-13 and compressive stress increased TF expression, but only compressive stress induced TF-positive extracellular vesicle release. Pretreatment with IL-13 augmented compressive stress-induced TF expression and release. TF protein and activity in BAL fluid were increased in allergen-sensitized and -challenged mice. TF was elevated in the BAL fluid of patients with mild asthma after an allergen challenge. Our in vitro and in vivo data indicate close cooperation between mechanical and inflammatory stimuli on TF expression and release of TF-positive extracellular vesicles in the lungs, which may contribute to pathophysiology of asthma.Keywords: asthma; bronchoconstriction; mechanotransduction; coagulation; airway epithelium Clinical RelevanceTwo critical components of asthma-IL-13 and bronchoconstriction-cooperatively work to induce tissue factor (TF) expression and release of TF-positive extracellular vesicles from well-differentiated human bronchial epithelial cells. Furthermore, in both mice and humans, allergen challenge increases the release of TF into bronchoalveolar lavage fluid.Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness (1, 2). Although the immune system is certainly implicated in asthma, a growing body of evidence suggests that airway epithelial cells also initiate and perpetuate disease (3, 4). During asthma exacerbations, airway smooth muscle contracts excessively and the airway becomes narrowed, resulting in buckling of the airway epithelium (5, 6). Epithelial cells in such buckled airways are subjected to a compressive mechanical stress of approximately 30 cm H 2 O (7). Using an in vitro system mimicking the Correspondence and requests for reprints should be addressed to Jin

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Section: Compressive Stress Increases Tf Mrna Expression In Nhbe Cellmentioning

confidence: 92%

Section: Tf Is Elevated In the Bal Fluid Of Ova-challenged Micementioning

confidence: 94%

Section: Compressive Stress Increases Tf Mrna Expression In Nhbe Cellmentioning

confidence: 99%

mentioning

confidence: 99%

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IL-13 Augments Compressive Stress–Induced Tissue Factor Expression in Human Airway Epithelial Cells

Mitchel¹,

Antoniak

Kim

et al. 2016

Am J Respir Cell Mol Biol

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“…They may also contribute to the inflammation and remolding of the asthma airway (9,10). Mononuclear cells are the key cell type to express TF and are the primary source of blood-borne TF in vitro and in vivo (11).…”

Section: Introductionmentioning

confidence: 99%

TIPE2 is negatively correlated with tissue factor and thrombospondin-1 expression in patients with bronchial asthma

et al. 2018

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Abstract. The interaction between inflammatory processes and a hypercoagulant state may aggravate the severity of asthma and stimulate the airway remodeling of asthma. The aim of the current study was to evaluate the association between the negative inflammatory regulator tumor necrosis factor α induced protein-8 like-2 (TIPE2) and the coagulating substances tissue factor (TF) and thrombospondin-1 (TSP-1) in patients with bronchial asthma. Compared with healthy controls, TIPE2 expression was significantly downregulated, whereas TF expression was upregulated in the peripheral blood mononuclear cells (PBMCs) of patients with bronchial asthma. In addition, levels of TF and TSP-1 in the sera were up-regulated in patients with asthma compared with healthy controls. TIPE2 expression was negatively correlated with TF in the PBMCs and sera and was negatively correlated with TSP-1 levels in the sera of patients with bronchial asthma. The results of the current study indicated that anti-inflammatory TIPE2 levels are associated with levels of the coagulation substances TF and TSP-1. However, further studies are required to determine whether TIPE2 participates in the pathogenesis of asthma by interacting with the coagulation substances TF and TSP-1.

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Exosomes in asthma: Underappreciated contributors to the pathogenesis and novel therapeutic tools

Kanannejad,

Arab,

Soleimanian

et al. 2024

Immunity Inflam & Disease

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ObjectiveAsthma, a chronic inflammatory disease with diverse pathomechanisms, presents challenges in developing personalized diagnostic and therapeutic approaches. This review aims to provide a comprehensive overview of the role of exosomes, small extracellular vesicles, in asthma pathophysiology and explores their potential as diagnostic biomarkers and therapeutic tools.MethodsA literature search was conducted to identify recent studies investigating the involvement of exosomes in asthma. The retrieved articles were analyzed to extract relevant information on the role of exosomes in maintaining lung microenvironment homeostasis, regulating inflammatory responses, and their diagnostic and therapeutic potential for asthma.ResultsExosomes secreted by various cell types, have emerged as crucial mediators of intercellular communication in healthy and diseased conditions. Evidence suggest that exosomes play a significant role in maintaining lung microenvironment homeostasis and contribute to asthma pathogenesis by regulating inflammatory responses. Differential exosomal content between healthy individuals and asthmatics holds promise for the development of novel asthma biomarkers. Furthermore, exosomes secreted by immune and nonimmune cells, as well as those detected in biofluids, demonstrate potential in promoting or regulating immune responses, making them attractive candidates for designing new treatment strategies for inflammatory conditions such as asthma.ConclusionExosomes, with their ability to modulate immune responses and deliver therapeutic cargo, offer potential as targeted therapeutic tools in asthma management. Further research and clinical trials are required to fully understand the mechanisms underlying exosome‐mediated effects and translate these findings into effective diagnostic and therapeutic strategies for asthma patients.

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Tissue factor–bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo

Cited by 99 publications

References 45 publications

IL-13 Augments Compressive Stress–Induced Tissue Factor Expression in Human Airway Epithelial Cells

IL-13 Augments Compressive Stress–Induced Tissue Factor Expression in Human Airway Epithelial Cells

TIPE2 is negatively correlated with tissue factor and thrombospondin-1 expression in patients with bronchial asthma

Exosomes in asthma: Underappreciated contributors to the pathogenesis and novel therapeutic tools

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