Tag: eosinophil

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

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The soluble guanylyl cyclase activator BAY 60-2770 inhibits murine allergic airways inflammation and human eosinophil chemotaxis.

Pulm Pharmacol Ther. 2016 Nov 2;:

Authors: Baldissera L, Squebola-Cola DM, Calixto MC, Lima-Barbosa AP, Rennó AL, Anhê GF, Condino-Neto A, De Nucci G, Antunes E

Abstract
OBJECTIVES: Activators of soluble guanylyl cyclase (sGC) act preferentially in conditions of enzyme oxidation or haem group removal. This study was designed to investigate the effects of the sGC activator BAY 60-2770 in murine airways inflammation and human eosinophil chemotaxis.
METHODS: C57Bl/6 mice treated or not with BAY 60-2770 (1 mg/kg/day, 14 days) were intranasally challenged with ovalbumin (OVA). At 48 h, bronchoalveolar lavage fluid (BALF) was performed, and circulating blood, bone marrow and lungs were obtained. Human eosinophils purified from peripheral blood were used to evaluate the cell chemotaxis.
RESULTS: OVA-challenge promoted marked increases in eosinophil number in BAL, lung tissue, circulating blood and bone marrow, all of which were significantly reduced by BAY 60-2770. The IL-4 and IL-5 levels in BALF were significantly reduced by BAY 60-2770. Increased protein expression of iNOS, along with decreases of expression of sGC (?1 and ?1 subunits) and cGMP levels were detected in lung tissue of OVA-challenged mice. BAY 60-2770 fully restored to baseline the iNOS and sGC subunit expressions, and cGMP levels. In human isolated eosinophils, BAY 60-2770 (1-5 ?M) had no effects on the cGMP levels and eotaxin-induced chemotaxis; however, prior incubation with ODQ (10 ?M) markedly elevated the BAY 60-2770-induced cyclic GMP production, further inhibiting the eosinophil chemotaxis.
CONCLUSIONS: BAY 60-2770 reduces airway eosinophilic inflammation and rescue the sGC levels. In human eosinophils under oxidized conditions, BAY 60-2770 elevates the cGMP levels causing cell chemotaxis inhibition. BAY 60-2770 may reveal a novel therapeutic target for asthma treatment.

PMID: 27816773 [PubMed – as supplied by publisher]

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Predicting frequent asthma exacerbations using blood eosinophil count and … – Dove Medical Press

Predicting frequent asthma exacerbations using blood eosinophil count and …
Dove Medical Press
Patients and methods: Medical records of 130,547 asthma patients aged 12–80 years from the UK Optimum Patient Care Research Database and Clinical Practice Research Datalink, 1990–2013, were examined for 1 year before (baseline) and 1 year after …

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SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients.

SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients.

Int J Mol Sci. 2015;16(3):5434-5451

Authors: Zafra MP, Cañas JA, Mazzeo C, Gámez C, Sanz V, Fernández-Nieto M, Quirce S, Barranco P, Ruiz-Hornillos J, Sastre J, Del Pozo V

Abstract
Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process.

PMID: 25764157 [PubMed – as supplied by publisher]

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Anti-IL-5 Cuts Exacerbations in Eosinophil Asthma – MedPage Today


Scicasts (press release) (registration) (blog)

Anti-IL-5 Cuts Exacerbations in Eosinophil Asthma
MedPage Today
In one of the studies, the clinical asthma exacerbation (CAE) rate was halved (rate ratio 0.50, 95% CI 0.37-0.67, P<0.0001) among patients receiving reslizumab compared with those given placebo, reported Mario Castro, MD, MPH, of Washington University …
Investigational drug can reduce asthma flareupsMedical Xpress
Investigational biologics among emerging therapies for severe asthmaHealio
Investigational Drug Could Reduce Asthma FlareupsScicasts (press release) (registration) (blog)
MarketWatch
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Elevated eosinophil levels increased risk for asthma exacerbation – Healio

Elevated eosinophil levels increased risk for asthma exacerbation
Healio
Adults with persistent asthma who had elevated eosinophil levels were at increased risk for exacerbations, according to research presented at the 2014 American Thoracic Society International Conference in San Diego. “Eosinophils are known to be …
Elevated blood eosinophil levels find to be risk factor for exacerbations in …News-Medical.net
Eosinophils linked to worsening asthmaOnMedica

all 3 news articles »

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Elevated blood eosinophil levels are a risk factor for asthma exacerbations – EurekAlert (press release)

Elevated blood eosinophil levels are a risk factor for asthma exacerbations
EurekAlert (press release)
ATS 2014, SAN DIEGO ? In adults with persistent asthma, elevated blood eosinophil levels may be able to predict which individuals are at increased risk for exacerbations, according to a new study presented at the 2014 American Thoracic Society …

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Elevated blood eosinophil levels are a risk factor for asthma exacerbations – Medical Xpress

Elevated blood eosinophil levels are a risk factor for asthma exacerbations
Medical Xpress
In adults with persistent asthma, elevated blood eosinophil levels may be able to predict which individuals are at increased risk for exacerbations, according to a new study presented at the 2014 American Thoracic Society International Conference.

and more »

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Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils.

Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils.

J Leukoc Biol. 2013 Apr 29;

Authors: Doyle AD, Jacobsen EA, Ochkur SI, Willets L, Shim K, Neely J, Kloeber J, Lesuer WE, Pero RS, Lacy P, Moqbel R, Lee NA, Lee JJ

Abstract
Eosinophils are generally linked to innate host defense against helminths, as well as the pathologies associated with allergic diseases, such as asthma. Nonetheless, the activities of eosinophils remain poorly understood, which in turn, has prevented detailed definitions of their role(s) in health and disease. Homologous recombination in embryonic stem cells was used to insert a mammalianized Cre recombinase in the ORF encoding Epx. This knock-in strategy overcame previous inefficiencies associated with eosinophil-specific transgenic approaches and led to the development of a knock-in strain of mice (eoCRE), capable of mediating recombination of “floxed” reporter cassettes in >95% of peripheral blood eosinophils. We also showed that this Cre expression was limited exclusively to eosinophil-lineage committed cells with no evidence of Cre-mediated toxicity. The efficiency and specificity of Cre expression in eoCRE mice were demonstrated further in a cross with a knock-in mouse containing a “(flox-stop-flox)” DTA cassette at the ROSA26 locus, generating yet another novel, eosinophil-less strain of mice. The development of eoCRE mice represents a milestone in studies of eosinophil biology, permitting eosinophil-specific gene targeting and overexpression in the mouse as part of next-generation studies attempting to define eosinophil effector functions.

PMID: 23630390 [PubMed – as supplied by publisher]

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