Pollen proteases compromise the airway epithelial barrier through degradation of transmembrane adhesion proteins and lung bioactive peptides

Vinhas, Raquel; Cortes, Luísa; Cardoso, Isabel; Mendes, Vera M.; Manadas, Bruno; Todo-Bom, Ana; Pires, Euclides; Verı́ssimo, Paula

doi:10.1111/j.1398-9995.2011.02598.x

Cited by 126 publications

(109 citation statements)

References 33 publications

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“…Finally, PAR stimulation opens tight junctions (TJ) by the secretion of metalloproteinase 9 [56]. Furthermore, it was described that some pollen grains release proteases with serine and/or amino peptidase activity which cleave transmembrane adhesion proteins facilitating para-cellular allergen delivery across Calu-3 human EC line and likely contributing to allergic sensitization [57]. Interestingly, in a recent study the protease activity of allergens was directly linked to TLR4 activation.…”

Section: Effect Of Proteases On the Epithelial Barriermentioning

confidence: 99%

What makes an allergen?

Scheurer

Toda

Vieths

2015

Clin Experimental Allergy

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SummaryAllergic diseases are an immune disorder reacting to certain type of allergen(s). Remarkably only a small number of proteins of the plant and animal proteome act as allergens. Therefore, allergens have been clustered according to their common structural, biochemical and functional features. Evidence has accumulated that some allergens possess intrinsic adjuvant properties to stimulate the innate immunity. The adjuvant properties appear to contribute to the allergenicity of the respective proteins, namely the ability to cause allergic sensitization in susceptible subjects or allergic reactions in sensitized individuals. Here, we discuss how allergens interact with the innate immune cells, in particular dendritic cells and epithelial cells, via binding to pattern recognition receptors, exhibiting proteolytic activities and/or inducting type 2 innate lymphoid cells (ILC2), thereby contributing to the sensitization and development of allergic diseases.

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Section: Effect Of Proteases On the Epithelial Barriermentioning

confidence: 99%

What makes an allergen?

Scheurer

Toda

Vieths

2015

Clin Experimental Allergy

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“…While 16HBE 14o-cells have been reported to exhibit morphological features including apical microvilli and cilia (Cozens et al, 1994), in our experience cilia are absent from polarized 16HBE 14o-cultures. In addition to their use for toxicology (Forti et al, 2010(Forti et al, , 2011 and drug transport studies, 16HBE 14o-and Calu-3 cell lines are frequently used for analysis of pathways involved in barrier function in response to environmental agents including allergens (Vinhas et al, 2011;Wan et al, 2001), particulates (Banga et al, 2012), cigarette smoke (Heijink et al, 2012) or viral infections (Harcourt et al, 2011;Rezaee et al, 2011). The other frequently used bronchial epithelial cell line, BEAS2B (Reddel et al, 1988), is not of value for transport studies as it fails to form an appreciable barrier (Forbes and Ehrhardt, 2005).…”

Section: Cfdeo-/6rep-cftrmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

124

103

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SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

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“…It has previously been reported that proteases and lipid components of pollen extracts have the potential to interfere with the barrier functions of bronchial epithelial cells [14,15,20]. For example, pollen from Giant Ragweed, White Birch, Kentucky Blue Grass or Easter Lily have been shown to disrupt epithelial tight junctions with loss of occludin, ZO-1 and claudin-1 from the junctions [15].…”

Section: Figurementioning

confidence: 99%

“…Besides their modulatory effect on immune cells [13], components of pollen also have the potential to affect the epithelial barrier. Using epithelial cell lines, such as Calu-3, it has been suggested that proteases released by pollen interfere with epithelial barrier functions [14,15]. However, these cell line-based models do not recapitulate the in vivo epithelium: they are undifferentiated, lacking cilia, goblet cells and mucus secretions that protect the cell surface from components of the inhaled environment [16].…”

Section: Introductionmentioning

confidence: 99%

Barrier responses of human bronchial epithelial cells to grass pollen exposure

et al. 2012

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The airway epithelium forms a physical, chemical and immunological barrier against inhaled environmental substances. In asthma, these barrier properties are thought to be abnormal. In this study, we analysed the effect of grass pollen on the physical and immunological barrier properties of differentiated human primary bronchial epithelial cells.Following exposure to Timothy grass (Phleum pratense) pollen extract, the integrity of the physical barrier was not impaired as monitored by measuring the transepithelial resistance and immunofluorescence staining of tight junction proteins. In contrast, pollen exposure affected the immunological barrier properties by modulating vectorial mediator release. CXC chemokine ligand (CXCL)8/interleukin (IL)-8 showed the greatest increase in response to pollen exposure with preferential release to the apical compartment. Inhibition of the extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase pathways selectively blocked apical CXCL8/IL-8 release via a post-transcriptional mechanism. Apical release of CC chemokine ligand (CCL)20/macrophage inflammatory protein-3a, CCL22/monocyte-derived chemokine and tumour necrosis factor-a was significantly increased only in severe asthma cultures, while CCL11/eotaxin-1 and CXCL10/interferon-c-induced protein-10 were reduced in nonasthmatic cultures.The bronchial epithelial barrier modulates polarised release of mediators in response to pollen without direct effects on its physical barrier properties. The differential response of cells from normal and asthmatic donors suggests the potential for the bronchial epithelium to promote immune dysfunction in asthma. @ERSpublications Bronchial epithelial barrier response to pollen exposure: does bronchial epithelium promote immune dysfunction in asthma?

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Pollen proteases compromise the airway epithelial barrier through degradation of transmembrane adhesion proteins and lung bioactive peptides

Abstract: Pollen grains with distinct allergenic abilities release proteases that might be involved in the sensitization to a range of airborne allergens by facilitating allergen delivery across the epithelium and also contribute directly to the inflammation characteristic of allergic diseases.

Cited by 126 publications

References 33 publications

What makes an allergen?

What makes an allergen?

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Barrier responses of human bronchial epithelial cells to grass pollen exposure

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