Published ahead of print on June 9, 2005, doi:10.1165/rcmb.2005-0067OC
American Journal of Respiratory Cell and Molecular Biology. Vol. 33, pp. 203-210, 2005
© 2005 American Thoracic Society DOI: 10.1165/rcmb.2005-0067OC
Mechanical Stretch Alters Alveolar Type II Cell Mediator Release toward a Proinflammatory Pattern
Stefan Hammerschmidt*,
Hartmut Kuhn*,
Ulrich Sack,
Anke Schlenska,
Christian Gessner,
Adrian Gillissen and
Hubert Wirtz
Department of Respiratory Medicine and Critical Care, and Department of Immunology, University of Leipzig; and Robert-Koch-Klinik, Leipzig, Germany
Correspondence and requests for reprints should be addressed to PD Dr. Stefan Hammerschmidt, Medizinische Universitätsklinik I, Pneumologie, Universität Leipzig, Johannisallee 32, 04103 Leipzig, Germany. E-mail: stefan.hammerschmidt{at}t-online.de
Increased mechanical stretch of alveolar type II (ATII) cells occurs during mechanical ventilation. The effects of three patterns of stretching rat ATII cells (frequency [min-1]- surface area [%]: S40-13, S60-13, S40-30) were compared with those in static cultures at 12, 18, and 24 h. Cell viability and expression of cyclooxygenase-2,5-lipoxygenase, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) were characterized. Supernatants were analyzed for eicosanoids, nitrite, cytokines, and stimulatory effects on rat lymphocytes. S40-13 simulates normal breathing; the other patterns increased amplitude and frequency. There were no significant differences between S40-13 and static cultures. S60-13 only significantly increased the supernatant nitrite (11.2 ± 1.6 versus 3.9 ± 0.4 µM at 24 h). S40-30 significantly reduced the number of trypan blueexcluding cells, increased the supernatant concentration of TXB2 (4.1 ± 0.61 versus 2.2 ± 0.36 pg/ml), 6-keto-PGF1 (8.7 ± 1.0 versus 6.7 ± 0.52 pg/ml), cysteinyl-LT (12.2 ± 2.0 versus 6.1 ± 0.75 pg/ml) and nitrite (7.2 ± 1.7 versus 3.9 ± 0.4 µM). S40-30 did not alter the release of tumor necrosis factor- and monocyte chemotactic protein-1, but significantly reduced the concentration of the anti-inflammatory interleukin-10 (20.8 ± 13.3 versus 130 ± 21.5 pg/ml). Expression of cyclooxygenase-2/5-lipoxygenase was increased/decreased; expression of iNOS/eNOS was unchanged by high-amplitude stretch. Supernatants from S40-30 experiments caused lymphocyte activation measured by CD71 and CD54 surface expression. Continuing mechanical distension of ATII cells contributes to an inflammatory response by a shift in the balance of pro- and anti-inflammatory mediators.
Key Words: alveolar type II cell mechanical stretch mediator release
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