Apoptosis and necrosis induced by cyclic mechanical stretching in alveolar type II cells.
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 microg/ml and 0.177 +/- 0.050 microg/ml versus 0.050 +/- 0.011 microg/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.
Hammerschmidt
Stefan
S
Department of Respiratory Medicine and Critical Care, University of Leipzig, Johannisallee 32, 04103 Leipzig, Germany. stefan.hammerschmidt@t-online.de
Kuhn
Hartmut
H
Grasenack
Thomas
T
Gessner
Christian
C
Wirtz
Hubert
H
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000959:Antihypertensive Agents / Q000494:pharmacology; D017209:Apoptosis; D001120:Arginine / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008297:Male; D009336:Necrosis; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
D017304:Annexin A5; D000959:Antihypertensive Agents; D000804:Angiotensin II; D001120:Arginine; D002216:Captopril; D045022:Lactate Dehydrogenases; C505528:Casp8 protein, rat; D053181:Caspase 8; D020169:Caspases