TY - JOUR T1 - Remodelling of cytoskeleton towards a softer cell by latrunculin prevents stretch-induced apoptosis in alveolar type II cells JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - P820 AU - Hartmut Kuhn AU - Thomas Fuchs AU - Franziska Wetzel AU - Stephan Hammerschmidt AU - Josef A. Käs AU - Hubert Wirtz Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/P820.abstract N2 - Background: Cyclic stretching of alveolar type II (ATII) cells is associated with alterations of the actin cytoskeleton and has been shown to induce apoptosis.Objectives: We hypothesize that the cytoskeleton of ATII cells and its viscoelastic properties are involved in the mediation of high amplitude mechanical stretch-induced apoptosis. Therefore we investigated the influence of the actin-modulating drug Latrunculin D on viscoelastic properties and stretch-induced apoptosis of ATII cells.Methods: Alveolar type II (ATII) cells from Sprague Dawley rats were exposed to cyclic stretching using a pattern characterized by frequency of 40 [min-1] and an amplitude of 30 [%]. During stretching cells were treated with Latrunculin D. After stretching we determined apoptosis and cell injury using an Annexin V-FITC Apoptosis Detection Kit and the Cytotoxicity Detection kit. Further, elasticity measurements of Latrunculin treated cells were performed with the atomic force microscope (AFM) and the optical stretcher.Results: Determination of elastic modulus using the AFM showed that Latrunculin reduced stiffness of ATII cells (83,5%). Using the optical stretcher ATII cells treated with Latrunculin showed a higher deformation than controls (25,3%). Treatment of overstretched cells with Latrunculin reduced significant the number of apoptotic cells (control 30,0%, Latrunculin 19,1%) and decrease the level of LDH (control 0,21 U/ml; Latrunculin 0,13 U/ml).Conclusions: We conclude that the remodelling of cytoskeleton toward a softer cell is a protective mechanism against stretch-induced apoptosis in ATII cells. ER -