Attachment of columnar airway epithelial cells in asthma

Shebani, Eyman; Shahana, Shahida; Janson, Christer; Roomans, Godfried M.

doi:10.1016/j.tice.2004.12.002

Cited by 25 publications

(19 citation statements)

References 21 publications

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“…26,[30][31][32] For many years, ''epithelial desquamation'' has been described as a pathological feature in asthma death, 33 but until recently, its significance has not been fully appreciated. 34,35 Bronchial biopsy studies from patients with asthma of increasing severity demonstrate not only physical damage to the columnar cell layer but also evidence for injury through the expression of cell stressors such as heat shock protein 70, 36 evidence for activation of the caspase enzyme cascade involved in apoptosis both in asthma 26,[37][38][39] and in a murine model of airway inflammation, 40 and enhanced surface expression of epidermal growth factor receptors (EGFRs), [41][42][43] as well as other receptors involved in innate immunity, including CD40 and TLRs. 44,45 These epithelial markers of stress and injury increase in proportion to disease severity and chronicity.…”

Section: The Epithelium In Orchestration Of the Asthmatic Responsementioning

confidence: 99%

Epithelium dysfunction in asthma

Holgate

2007

Journal of Allergy and Clinical Immunology

441

326

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Section: The Epithelium In Orchestration Of the Asthmatic Responsementioning

confidence: 99%

Epithelium dysfunction in asthma

Holgate

2007

Journal of Allergy and Clinical Immunology

441

326

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“…Airway epithelial cells (AEC) are continuously exposed to and injured by environmental irritants, such as viruses and pollutants, and as such are ideally situated to orchestrate airway function in response to these stimuli. We and others have shown that the epithelium is intrinsically altered both structurally and biochemically in asthma, reflecting an increased susceptibility to injury, an inadequate repair response, or a combination of both (7)(8)(9)(10)(11)(12)(13)(14). Importantly, many of the characteristic abnormalities can be detected early in disease progression and correlate with disease severity (15).…”

mentioning

confidence: 97%

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Kicic¹,

Hallstrand²,

Sutanto³

et al. 2010

Am J Respir Crit Care Med

137

154

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Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from children with asthma fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n 5 36), healthy atopic control subjects (n 5 23), and healthy nonatopic control subjects (n 5 53) were investigated by microarray, gene expression and silencing, transcript regulation analysis, and ability to close mechanical wounds. Measurements and Main Results: Time to repair a mechanical wound in vitro by AEC from healthy and atopic children was not significantly different and both were faster than AEC from children with asthma. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by quantitative polymerase chain reaction and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in nonasthmatic AEC inhibited wound repair, whereas addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/ growth factor stimulation. Exposure to 59, 29deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells.

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“…Prior investigations have implicated the role of epithelial cells in initiating asthma (31,35) and atopic responsiveness (32). Although cytokines (IL-1␤, GM-CSF), chemokines (RANTES, IL-8) and other soluble factors (platelet-activating factor, platelet-derived growth factor) are secreted from epithelial cells, these compounds have a modest effect, if any, on eosinophil secretion of LTC 4 .…”

Section: Discussionmentioning

confidence: 99%

“…2B). Although hIbPLA 2 has no hydrolytic activity for inflammatory cells (3,31), hXPLA 2 and Naja naja naja PLA 2 have been shown to bind and hydrolyze the outer PC plasma membrane of granulocytes. These isoforms, however, have no capacity for uptake into mammalian cells due to their low affinity for cell surface heparan sulfate proteoglycan (HSPG) (3,7,23,26).…”

Section: Effect Of Purified Secretory Pla 2 Isozymes On Cell Adhesionmentioning

confidence: 99%

Transcellular Secretion of Group V Phospholipase A2 from Epithelium Induces β2-Integrin-Mediated Adhesion and Synthesis of Leukotriene C4 in Eosinophils

Muñoz

Meliton

Lambertino

et al. 2006

The Journal of Immunology

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We examined the mechanism by which secretory group V phospholipase A2 (gVPLA2) secreted from stimulated epithelial cells activates eosinophil adhesion to ICAM-1 surrogate protein and secretion of leukotriene (LT)C4. Exogenous human group V PLA2 (hVPLA2) caused an increase in surface CD11b expression and focal clustering of this integrin, which corresponded to increased β2 integrin-mediated adhesion. Human IIaPLA2, a close homolog of hVPLA2, or W31A, an inactive mutant of hVPLA2, did not affect these responses. Exogenous lysophosphatidylcholine but not arachidonic acid mimicked the β2 integrin-mediated adhesion caused by hVPLA2 activation. Inhibition of hVPLA2 with MCL-3G1, a mAb against gVPLA2, or with LY311727, a global secretory phospholipase A2 (PLA2) inhibitor, attenuated the activity of hVPLA2; trifluoromethylketone, an inhibitor of cytosolic group IVA PLA2 (gIVA-PLA2), had no inhibitory effect on hVPLA2-mediated adhesion. Activation of β2 integrin-dependent adhesion by hVPLA2 did not cause ERK1/2 activation and was independent of gIVA-PLA2 phosphorylation. In other studies, eosinophils cocultured with epithelial cells were stimulated with FMLP/cytochalasin B (FMLP/B) and/or endothelin-1 (ET-1) before LTC4 assay. FMLP/B alone caused release of LTC4 from eosinophils, which was augmented by coculture with epithelial cells activated with ET-1. Addition of MCL-3G1 to cocultured cells caused ∼50% inhibition of LTC4 secretion elicited by ET-1, which was blocked further by trifluoromethylketone. Our data indicate that hVPLA2 causes focal clustering of CD11b and β2 integrin adhesion by a novel mechanism that is independent of arachidonic acid synthesis and gIVA-PLA2 activation. We also demonstrate that gVPLA2, endogenously secreted from activated epithelial cells, promotes secretion of LTC4 in cocultured eosinophils.

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Attachment of columnar airway epithelial cells in asthma

Cited by 25 publications

References 21 publications

Epithelium dysfunction in asthma

Epithelium dysfunction in asthma

Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium

Transcellular Secretion of Group V Phospholipase A2 from Epithelium Induces β2-Integrin-Mediated Adhesion and Synthesis of Leukotriene C4 in Eosinophils

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