RT Journal Article
SR Electronic
T1 Extracellular proteasomes are cAMP-dependent released by alveolar epithelial cells type II
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P518
VO 42
IS Suppl 57
A1 Stephan J. Schließmann
A1 Kerstin Höhne
A1 Timur Anlasik
A1 Matthias Schmidt
A1 Martin J. Hug
A1 Andreas Kirschbaum
A1 Joachim Müller-Quernheim
A1 Gernot Zissel
A1 Stephan U. Sixt
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P518.abstract
AB The repair mechanism resulting in alveolar protein degradation is largely unknown.In the alveolar space the presence of extracellular, biologically active proteasomes are recently reported [1,2]. The proteasome is involved in protein degradation and is able to degrade proteins at a high rate, possibly to minimize oncotic pressure [1].We tested proteasome release by alveolar epithelial cells type II (AEC-II).AEC-II were isolated from 24 macroscopically tumour-free lung tissues as described previously [3].Cells were stimulated with dibutyryl cAMP; for second part of the study after levelling with 1 µM indomethacin and 10 nM PGE2. Unstimulated AEC-II and primary isolated PBMC served as control. Extracellular proteasome concentration was measured by an established ELISA targeting the proteasome in supernatant. For statistical evaluation the Wilcoxon signed rank test was applied.Our study demonstrates for the first time that human non-tumourous AEC-II do release proteasomes. Stimulated with db-cAMP, the extracellular proteasome concentration (median unstim. 700 ng/mL) results in a wide insignificant range (median stim. 600 ng/ml). Indeed after levelling with indomethacin and PGE2 (median unstim. 400 ng/ml) the stimulation with db-cAMP. increases proteasome release highly significantly (stim. 460 ng/ml).Unchanged proteasome concentration in the alveolar fluid showed no artificial elution of the proteasomes by the pre-smoking lavage.In conclusion, AEC-II release proteasomes cAMP-dependent into the alveolar space.[1] Sixt, S.U. et al. Am J Physiol Lung Cell Mol Physiol 2007; 292:L1280-8[2] Sixt, S.U. et al. Am J Respir Crit Care Med 2009; 179:1098-106.[3] Hoehne, K. et al. PLoS One 2012; 7:e38369.