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Published ahead of print on September 4, 2003, doi:10.1165/rcmb.2003-0136OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 30, pp. 396-402, 2004
© 2004 American Thoracic Society
DOI: 10.1165/rcmb.2003-0136OC

Apoptosis and Necrosis Induced by Cyclic Mechanical Stretching in Alveolar Type II Cells

Stefan Hammerschmidt, Hartmut Kuhn, Thomas Grasenack, Christian Gessner and Hubert Wirtz

Department of Respiratory Medicine and Critical Care, University of Leipzig, Leipzig, Germany

Address correspondence to: Dr. Stefan Hammerschmidt, Medizinische Universitätsklinik I, Pneumologie, Universität Leipzig, Johannisallee 32, 04103 Leipzig, Germany. 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 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. Lactic acid dehydrogenase (LDH) release and early apoptotic cells were significantly increased in S60-13 and S40-30 in comparison with static cultures (LDH: 0.089 ± 0.014 µg/ml and 0.177 ± 0.050 µg/ml versus 0.050 ± 0.011 µg/ml; early apoptosis: 17 ± 3.5% and 23 ± 3.1% versus 9.7 ± 1.4%) at 24 h. Necrosis was significantly increased only in the S40-30 group (13 ± 2.4% versus 6.1 ± 0.9% in static culture at 24 h). 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.

Abbreviations: angiotensin converting enzyme, ACE • acute respiratory distress syndrome, ARDS • alveolar type II cell, ATII cell • Dulbecco's modified Eagle's medium, DMEM • epithelial basement membrane surface area, EBMSA • fetal calf serum, FCS • functional residual capacity, FRC • lactic acid dehydrogenase, LDH • nitric oxide, NO • nitric oxide synthase, NOS • propidium iodide, PI • total lung capacity, TLC




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