Mechanical stretch alters alveolar type II cell mediator release toward a proinflammatory pattern

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)]-Delta 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 (NOS), 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 mu M at 24 h). S40-30 significantly reduced the number of trypan blue-excluding cells, increased the supernatant concentration of TXB2 (4.1 +/- 0.61 versus 2.2 +/- 0.36 pg/ml), 6-keto-PGF1 alpha (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 mu M). S40-30 did not alter the release of tumor necrosis factor-a 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/eNCIS 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.