Mechanical stretch alters alveolar type II cell mediator release towards a pro-inflammatory 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]∆surface area [%]: S40-13, S60-13, S40-30) were compared with those in static cultures at 12/18/24h. Cell viability and expression of COX-2, 5-LO, iNOS, 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±0.4μM at 24h). S4030 significantly reduced the number of trypan blue excluding cells, increased the supernatant concentration of TXB2 (4.1±0,61 versus 2.2±0.36pg/ml), 6-keto-PGF1α (8.7±1.0 versus 6.7±0.52pg/ml), cysteinyl-LT (12.2±2.0 versus 6.1±0.75pg/ml) and nitrite (7.2±1.7 versus 3.9±0.4μM). S40-30 did not alter the release of TNFα and MCP-1 but significantly reduced the concentration of the anti-inflammatory IL-10 (20.8±13.3 versus 130±21.5pg/ml). Expression of COX-2/5-LO 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.