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

Ilmarinen, Pinja, James, Anna, Moilanen, Eeva, Pulkkinen, Ville, Daham, Kameran, Saarelainen, Seppo, Laitinen, Tarja, Dahlén, Sven-Erik, Kere, Juha, Dahlén, Barbro, Kankaanranta, Hannu
Peptides 2014 v.51 pp. 100-109
adhesion, agonists, asthma, blood serum, calcium, chemotaxis, cyclic AMP, eosinophils, genes, haplotypes, humans, immunoglobulin E, integrins, neuropeptides, patients, phenotype, protein synthesis, risk
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 Ca²⁺ 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.