Table 3.
Effect of LFA 703 on endotoxin-induced leukocyte recruitment and liver injury
| Leukocyte adhesion (cells mm−1) | Sinusoidal perfusion (%) | ALT (μKat l−1) | AST (μKat l−1) | Apoptosis (%) | |
|---|---|---|---|---|---|
| Control | 1.6±0.9 | 95±1 | 1.9±0.3 | 7.0±1.6 | 5.2±0.6 |
| Vehicle+LPS/Gal | 16.3±2.9# | 76.6±1.6# | 31.8±4.4# | 37.6±5.5# | 44.7±6.2# |
| 0.3+LPS/Gal | 11.4±2.0 | 80.0±2.9 | 35.4±9.6 | 26.7±6.0 | 38.4±4.6 |
| 3+LPS/Gal | 7.6±1.2* | 90.9±0.7* | 9.9±4.0* | 11.6±2.2* | 18.9±0.9* |
| 30+LPS/Gal | 5.6±0.9* | 89.6±0.7* | 10.1±2.8* | 14.6±3.0* | 23.9±1.6* |
Wild-type mice received a combination of LPS (10 μg) and D-galactosamine (Gal, 18 mg). Negative control animals received PBS (control) and positive controls received LFA703 vehicle (Vehicle). Animals were pretreated for 2 h with LFA 703 (0.3, 3 and 30 mg kg−1, i.p., n=6–12). The number of adherent leukocytes was determined in postsinusoidal venules, using intravital fluorescence microscopy. Sinusoidal perfusion is given as the percentage of observed sinusoids with functional perfusion. The levels of ALT and AST were determined spectrophotometrically. Hepatocyte apoptosis is given as the percentage of observed hepatocyte nuclei with morphological signs of apoptosis, that is, chromatin condensation and fragmentation, after administration of the fluorochrome Hoechst 33342. Data represent means±s.e.m. and n=5–12.
P<0.05 vs control
P<0.05 vs vehicle+LPS/Gal.