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Peptides. 2014 Jan;51:100-9. doi: 10.1016/j.peptides.2013.10.030. Epub 2013 Nov 13.

Enhanced expression of neuropeptide S (NPS) receptor in eosinophils from severe asthmatics and subjects with total IgE above 100IU/ml.

Author information

1
The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: pinja.ilmarinen@uta.fi.
2
Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Experimental Asthma and Allergy Research, The National Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: anna.james@ki.se.
3
The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland. Electronic address: eeva.moilanen@uta.fi.
4
Department of Medicine, Pulmonary Division, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. Electronic address: ville.pulkkinen@helsinki.fi.
5
Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Department of Lung and Allergy Research, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: kameran.daham@ki.se.
6
Department of Respiratory Medicine, Tampere University Hospital, Tampere, Finland. Electronic address: seppo.saarelainen@pshp.fi.
7
Department of Pulmonary Diseases and Clinical Allergology, Turku University Hospital and University of Turku, Turku, Finland. Electronic address: tarja.laitinen@helsinki.fi.
8
Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Experimental Asthma and Allergy Research, The National Institute for Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: sven-erik.dahlen@ki.se.
9
Research Programs Unit, Program for Molecular Neurology, University of Helsinki and Folkhälsan Institute of Genetics, Helsinki, Finland; Department of Biosciences and Nutrition and Clinical Research Centre, Karolinska Institutet, Stockholm, Sweden. Electronic address: juha.kere@ki.se.
10
Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Department of Lung and Allergy Research, Karolinska University Hospital Huddinge, Stockholm, Sweden. Electronic address: barbro.dahlen@ki.se.
11
The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland; Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland and University of Tampere, Tampere, Finland. Electronic address: hannu.kankaanranta@epshp.fi.

Abstract

Eosinophils are inflammatory cells of particular relevance to asthma exacerbations. Neuropeptide S (NPS) receptor was identified in a search for asthma susceptibility genes, where the risk haplotypes of the NPS receptor gene associated with total serum IgE above 100IU/ml and asthma. The aim of the present study was to investigate and compare expression of NPS receptor in human peripheral blood eosinophils derived from subjects with total serum IgE above and below 100IU/ml and patients with different phenotypes of asthma. Additionally, we aimed to study the function of NPS receptor in human eosinophils. We found higher NPS receptor protein expression in eosinophils derived from subjects with high IgE when compared to those from subjects with low IgE and the level of NPS receptor positively correlated with serum IgE. NPS receptor expression was also higher in eosinophils from patients with severe asthma than in cells from mild asthmatics or healthy controls. The receptor agonist NPS was a chemotactic agent for eosinophils. NPS also increased N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated CD11b integrin levels in eosinophils from subjects with high IgE. Furthermore, eosinophils from those subjects exhibited Ca(2+) mobilization but not cAMP rise in response to NPS. Altogether, NPS receptor may have a pathological role in individuals with severe asthma and/or elevated serum IgE levels as eosinophils from these patients express higher levels of NPS receptor protein and respond to NPS by enhanced migration and adhesion molecule expression.

KEYWORDS:

AIA; CD11b; EDN; EPO; GM-CSF; Ig; IgE; N-formyl-methionyl-leucyl-phenylalanine; NPS; NPS receptor; aspirin-intolerant asthma; asthma; cAMP; calcium; chemotaxis; eosinophil peroxidase; eosinophil-derived neurotoxin; eosinophils; fMLP; granulocyte macrophage-colony stimulating factor; immunoglobulin; neuropeptide S

PMID:
24239856
DOI:
10.1016/j.peptides.2013.10.030
[Indexed for MEDLINE]
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