RT Journal Article
SR Electronic
T1 Acid sphingomyelinase, a novel pathway for pulmonary vasoconstriction. Activation by apoptotic T cell microparticles and Fas ligand
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P313
VO 44
IS Suppl 58
A1 Javier Javier Moral-Sanz
A1 Daniel Morales-Cano
A1 Bianca Barreira
A1 Raffaella Soleti
A1 Laura Moreno
A1 Angel Cogolludo
A1 Ramaroson Andriantsitohaina
A1 Carmen Martinez
A1 Francisco Perez-Vizcaino
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P313.abstract
AB Microparticles (MPs) are small membrane vesicles released from stimulated and/or apoptotic cells. We hypothesized that MPs have acute effects on pulmonary vascular contractility and Kv channel function. MPs were isolated from T lymphocytes treated with actinomycin D. Small pulmonary arteries (PA) from male Wistar rats were mounted for contractile tension recording in a wire myograph. Potassium currents were recorded in PA smooth muscle cells (PASMC) using the patch clamp technique. MPs (10 mg protein/ml) reduced Kv current amplitude, depolarized PASMC and induced a slow developing sustained contraction in PA that was blunted by the L-type Ca2+ channel blocker nifedipine. MP-induced contraction was attenuated by the anticeramide antibody and by the acid sphingomyelinase (aSMase) inhibitor D-609, but not by the neutral sphingomyelinase (nSMase) inhibitor GW4869. Similar to MPs, FasL-induced contraction was attenuated by the anticeramide antibody and by D-609 but not by GW4869. MPs also increased reactive oxygen species (ROS) in human PASMC in culture and the contractile effect in PA was abolished by the ROS scavenger tiron. In conclusion, MPs from apoptotic T lymphocytes produce pulmonary vasoconstriction involving the activation of Fas, acid sphingomyelinase, increase in ROS and inhibition of Kv channels.