Source: International Congress 2014 – Cell biology 2014
Disease area: Airway diseases

Abstract

Background: Eosinophil accumulation into the airways is characteristic for most phenotypes of asthma. Spermine, spermidine and putrescine are ubiquitous cationic polyamines with basic functions related to nucleic acid packaging, DNA replication, apoptosis, transcription and translation. Polyamine levels are elevated in serum and sputum from patients with asthma suggesting a role in the disease. Objective: The aim of the present study was to examine if polyamines, especially spermine, regulate eosinophil survival which is a significant factor contributing to airway eosinophilia. Methods: Eosinophils were isolated from venous blood of eosinophilic donors. Apoptosis was determined by transmission electron microscopic (TEM) analysis and DNA fragmentation assay. Mitochondrial permeability transition (mPT) was determined by calcein/CoCl₂ staining. Luminescence and fluorometric assays were used to measure activities of caspases. Results: Apoptosis-related DNA fragmentation was prevented by spermine (10-1000 µM) and spermidine (100-1000 µM) but not putrescine. TEM analysis confirmed the survival-prolonging effect of spermine and showed that its efficiency in enhancing survival was close to that of GM-CSF. Spermine and spermidine inhibited also mitochondrial permeability transition (mPT) while putrescine had no effect. Futhermore, spermine reduced activities of caspases. Conclusions: The present results introduce spermine as a novel eosinophil survival-prolonging factor associated with asthma and the mechanism seems to involve inhibition of mitochondrial permeability transition and suppression of caspase activity.

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P. Ilmarinen, E. Moilanen, J. S. Erjefält, H. Kankaanranta (Tampere, Seinäjoki, Finland; Lund, Sweden). The polyamine spermine inhibits mitochondrial permeability transition (mPT) and apoptosis in human eosinophils. Eur Respir J 2014; 44: Suppl. 58, 3842

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