Published ahead of print on September 4, 2003, doi:10.1165/rcmb.2003-0136OC
Am. J. Respir. Cell Mol. Biol., Volume 30, Number 3, March 2004, 396-402
A more recent version of this article appeared on March 1, 2004
Submitted on April 14, 2003
Revised on September 2, 2003
Apoptosis and Necrosis induced by cyclic mechanical stretching in alveolar type II cells
Stefan Hammerschmidt1*, Hartmut Kuhn1, Thomas Grasenack1, Christian Gessner1, and Hubert Wirtz1
1 Medizinische Klinik I, Universitat Leipzig, Leipzig, Germany
* To whom correspondence should be addressed. E-mail: stefan.hammerschmidt{at}t-online.de.
Alveolar type II (ATII) cells are exposed to mechanical stretch during breathing and mechanical ventilation. Increased stretch may contribute to lung injury. The influence of three stretching patterns (characterized by frequency [min-1] - increase in surface area [%]: S40-13, S60-13, S40-30) on parameters of apoptosis, necrosis and membrane integrity of in rat ATII cells was compared with that in static cultures. The S40-13 stretching pattern simulated normal breathing. The other patterns were chosen to study increased amplitude and frequency. There were no significant differences between the S40-13 group and static cultures. LDH release and early apoptotic cells were significantly increased in S60-13 and S40-30 in comparison with static cultures (LDH: 0.089±0.014µg/ml and 0.177±0.050µg/ml versus 0.050±0.011µg/ml; early apoptosis: 17±3.5% and 23±3.1% versus 9.7±1.4%) at 24h. Necrosis was significantly increased only in the S40-30 group (13±2.4% versus 6.1±0.9% in static culture at 24h). Captopril as well as L-Arginine prevented apoptosis and reduced apoptotic cells to static culture levels in the S40-30 group but did not influence necrosis and LDH release. Increased mechanical stretch may contribute to lung injury by induction of apoptosis and necrosis in ATII cells. Apoptosis induced by high amplitude mechanical stretch is prevented by captopril and L-Arginine.
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