Asthma

Holgate, Stephen T.

doi:10.1016/b978-0-12-415847-4.00096-3

Cited by 6 publications

(6 citation statements)

References 231 publications

(153 reference statements)

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Section: Hdps In Health and Diseasementioning

confidence: 99%

“…Asthma is the most common inflammatory condition of the lung and, when triggered by dust or allergens, leads to airway inflammation and airflow obstruction (Holgate et al, 2015). The exact cause of asthma is thought to involve a range of environmental and genetic factors; however, one of the features of this diseases is an altered innate immune response (Holgate et al, 2015). Allergic airway inflammation has been shown to suppress innate host defenses in mouse models of asthma, including reducing levels of the mouse cathelicidin CRAMP (Beisswenger et al, 2006).…”

Section: Hdps In Health and Diseasementioning

confidence: 99%

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Reassessing the Host Defense Peptide Landscape

2019

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Current research has demonstrated that small cationic amphipathic peptides have strong potential not only as antimicrobials, but also as antibiofilm agents, immune modulators, and anti-inflammatories. Although traditionally termed antimicrobial peptides (AMPs) these additional roles have prompted a shift in terminology to use the broader term host defense peptides (HDPs) to capture the multi-functional nature of these molecules. In this review, we critically examined the role of AMPs and HDPs in infectious diseases and inflammation. It is generally accepted that HDPs are multi-faceted mediators of a wide range of biological processes, with individual activities dependent on their polypeptide sequence. In this context, we explore the concept of chemical space as it applies to HDPs and hypothesize that the various functions and activities of this class of molecule exist on independent but overlapping activity landscapes. Finally, we outline several emerging functions and roles of HDPs and highlight how an improved understanding of these processes can potentially be leveraged to more fully realize the therapeutic promise of HDPs.

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Section: Hdps In Health and Diseasementioning

confidence: 99%

Section: Hdps In Health and Diseasementioning

confidence: 99%

Reassessing the Host Defense Peptide Landscape

2019

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“…Significantly elevated gene levels of CCL26 are found in eosinophilia-associated diseases, such as eosinophilic esophagitis and eosinophilic gastritis, where transepithelial migration of eosinophils is one of the key steps for pathogenesis [ 10 , 11 , 12 ]. Infiltrated eosinophils release proinflammatory, tissue-damaging, cytotoxic compounds, such as major basic proteins 1 and 2, eosinophil-derived neurotoxin, peroxidase, and eosinophilic cationic proteins [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Heparan Sulfate in CCL26-Induced Eosinophil Chemotaxis

Pum

Ennemoser

Gerlza

et al. 2022

IJMS

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Proinflammatory chemokine ligand 26 (CCL26, eotaxin-3) mediates transendothelial cell migration of eosinophils by binding and activating the G-protein-coupled (GPC) chemokine receptor 3 on the surface of eosinophilic cells. Here we have investigated the role of glycosaminoglycans (GAGs) as potential co-receptors in the process of CCL26-induced eosinophil chemotaxis. For this purpose, we have first identified the GAG-binding site of CCL26 by a site-directed mutagenesis approach in the form of an alanine screening. A panel of GAG-binding-deficient mutants has been designed, generated, and analyzed with respect to their binding affinities to heparan sulphate (HS) by isothermal fluorescence titration studies. This showed that basic amino acids in the α-helical part of CCL26 are strongly involved in GAG-binding. In chemotaxis experiments, we found that decreased GAG-binding affinity correlated with decreased chemotactic activity, which indicates an involvement of GAGs in eosinophil migration. This was further proven by the negative impact of heparinase III treatment and, independently, by the incubation of eosinophils with an anti heparan sulfate antibody. We finally investigated eosinophils’ proteoglycan (PG) expression patterns by real-time PCR, which revealed the highest expression level for serglycin. Including an anti-serglycin antibody in CCL26-induced eosinophil migration experiments reduced the chemotaxis of these immune cells, thereby proving the dependence of eosinophil mobilization on the proteoglycan serglycin.

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“…Around 80% of childhood-onset asthma and more than 50% of asthmatic adult patients suffer from allergic asthma ( 6 ). It has an early onset, usually in childhood, that commonly persists throughout life ( 3 , 7 ), and is characterized by a type 2 inflammatory profile, dominated by IL-4, IL-5, IL-9 and IL-13, Th2 cells, eosinophils, and IgE producing plasma cells ( 8 ). On the other hand, non-allergic or intrinsic asthma is poorly understood ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

“…Thus, these proteins might be able to, first, damage the epithelium, and then, activate the immune system, eliciting an immune response, especially in children with an immature epithelial barrier. In fact, respiratory infections in childhood are associated with a higher risk of developing asthma ( 7 ). Moreover, it has been recently described that Der p 1 elicits a differential metabolic response in an in vitro model of lung epithelium between underdeveloped (2 days of culture) and mature (7 days of culture) tissue ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Contribution of allergy in the acquisition of uncontrolled severe asthma

et al. 2022

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Asthma is a multifactorial, heterogeneous disease that has a challenging management. It can be divided in non-allergic and allergic (usually associated with house dust mites (HDM) sensitization). There are several treatments options for asthma (corticosteroids, bronchodilators, antileukotrienes, anticholinergics,…); however, there is a subset of patients that do not respond to any of the treatments, who can display either a T2 or a non-T2 phenotype. A deeper understanding of the differential mechanisms underlying each phenotype will help to decipher the contribution of allergy to the acquisition of this uncontrolled severe phenotype. Here, we aim to elucidate the biological pathways associated to allergy in the uncontrolled severe asthmatic phenotype. To do so, twenty-three severe uncontrolled asthmatic patients both with and without HDM-allergy were recruited from Hospital Universitario de Gran Canaria Dr. Negrin. A metabolomic fingerprint was obtained through liquid chromatography coupled to mass spectrometry, and identified metabolites were associated with their pathways. 9/23 patients had uncontrolled HDM-allergic asthma (UCA), whereas 14 had uncontrolled, non-allergic asthma (UCNA). 7/14 (50%) of the UCNA patients had Aspirin Exacerbated Respiratory Disease. There were no significant differences regarding gender or body mass index; but there were significant differences in age and onset age, which were higher in UCNA patients; and in total IgE, which was higher in UCA. The metabolic fingerprint revealed that 103 features were significantly different between UCNA and UCA (p < 0.05), with 97 being increased in UCA and 6 being decreased. We identified lysophosphocholines (LPC) 18:2, 18:3 and 20:4 (increased in UCA patients); and deoxycholic acid and palmitoleoylcarnitine (decreased in UCA). These metabolites were related with a higher activation of phospholipase A2 (PLA2) and other phospholipid metabolism pathways. Our results show that allergy induces the activation of specific inflammatory pathways, such as the PLA2 pathway, which supports its role in the development of an uncontrolled asthma phenotype. There are also clinical differences, such as higher levels of IgE and earlier onset ages for the allergic asthmatic group, as expected. These results provide evidences to better understand the contribution of allergy to the establishment of a severe uncontrolled phenotype.

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Asthma

Cited by 6 publications

References 231 publications

Reassessing the Host Defense Peptide Landscape

Reassessing the Host Defense Peptide Landscape

The Role of Heparan Sulfate in CCL26-Induced Eosinophil Chemotaxis

Contribution of allergy in the acquisition of uncontrolled severe asthma

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