Control | ANTU | LPS | P. aeruginosa | Effect of LY311727 in P. aeruginosa-instilled rats | |||||
6 or 24 h | 6 h | 24 h | 6 h | 24 h | 6 h | 24 h | 6 h | 24 h | |
Total BAL fluid cell count 1×104 | 90±19 | 61±9 | 111±21 | 2148±348*** | 1686±287*** | 2605±474*** | 2125±414*** | 1854±221 | 3707±559¶ |
Pa,O2 kPa | 13.2±0.7 | 11.4±0.5 | 11.2±1.1 | 10.1±0.3 | 11.6±0.3 | 8.9±2.3* | 10.1±0.8 | ND | ND |
W:D lung ratio | 3.9±0.1 | 4.7±0.1* | 4.3±0.1 | 4.6±0.2* | 4.5±0.1 | 6.2±0.5* | 4.2±0.1 | 6.3±0.5 | 5.1±1.1 |
Compliance rs mL·kPa−1 sPLA2-IIA activity | 3.23±0.18 | 2.81±0.10 | 1.80±0.43*** | 1.79±0.23*** | 2.64±0.11 | 1.94±0.14*** | 2.22±0.13* | 1.66±0.07 | 2.34±0.11 |
BAL fluid nmol·mL−1min−1 | 0.0±0.0 | 0.6±0.0 | 0.0±0.0 | 28.8±6.9*** | 15.5±7.1*** | 52.1±10.7*** | 24.0±5.3*** | 15.5±7.6# | 4.0±4.0¶ |
Lung homogenate nmol·mg−1·min−1 | 0.1±0.1 | 0.2±0.1 | 0.2±0.2 | 7.4±3.2 | 46.0±9.1 | 35.5±4.6 | 49.9±30.0 | 6.9±3.9 | 28.7±19.0 |
Each condition comprised six animals. Bronchoalveolar lavage (BAL) fluid cells were constituted mainly by alveolar macrophages (>95%) in both healthy rats and alpha naphthylthiourea (ANTU)-injured rats (no alveolar cell influx in this latter setting). By contrast, in lipopolysaccharide (LPS)- and bacteria-instilled rats alveolar influx of neutrophils that constituted >95% of total alveolar cells was observed
Pa,O2: arterial oxygen tension
rs: Spearman rank correlation coefficient
W:D: wet-to-dry weight lung ratio
sPLA2-IIA: specific type-II secretory phospholipase A2
ND: not determined
*: p<0.05 compared with healthy control rats
***: p<0.001 compared with healthy control rats
#: p<0.0001, and ¶: p<0.03 compared with bacteria-instilled rats without treatment by the sPLA2-IIA inhibitor (LY311727)