TY - JOUR T1 - The polyamine spermine prolongs eosinophil survival JF - European Respiratory Journal JO - Eur Respir J VL - 42 IS - Suppl 57 SP - P588 AU - Pinja Ilmarinen-Salo AU - Eeva Moilanen AU - Jonas S. Erjefält AU - Hannu Kankaanranta Y1 - 2013/09/01 UR - http://erj.ersjournals.com/content/42/Suppl_57/P588.abstract N2 - Background: Most phenotypes of asthma involve accumulation of eosinophils in the airways. 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 from patients with asthma suggesting a role in the disease. The aim of the present study was to investigate 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. Caspase 3/7, 8 and 9 activities were determined by luminescence assay. Results: We found that spermine (10-1000 µM) and spermidine (100-1000 µM) but not putrescine prevented apoptosis-related DNA fragmentation. Survival-prolonging effect of spermine was confirmed by TEM analysis, which showed that its efficiency in enhancing survival was close to that of GM-CSF. We also found that spermine repressed activities of caspases 3/7, 8 and 9. Inhibitor studies excluded JAK, PI3K, p38 and ERK1/2 as mediators of spermine-induced eosinophil survival. Additionally, spermine had no effect on LC3II expression indicating no role for autophagy in mediating its effects. Conclusions: In summary, our data show that spermine acts as an eosinophil survival-prolonging factor and the mechanism seems to involve inhibition of caspases 3/7, 8 and 9. The survival-promoting effects of spermine may contribute to the eosinophilia in asthma. ER -