Fig. 2

Time course of inflammation induced by intra-articular injection of MIA (0.3 mg/10 μl on day 0) and the effect of neutrophil elastase inhibition with sivelestat (50 mg/kg i.p., administered 10 min before and 240 min after MIA injection on day 0 and once on days 1 to 3) or serpinA1 (10 μg i.p., administered 15 min before and 12 h after MIA injection). a MIA induced a significant increase in knee joint diameter at 1, 3, 7 and 10 days post-injection that was blocked by systemic treatment with sivelestat (P < 0.0001, two-way ANOVA) or serpinA1 (P < 0.0001, two-way ANOVA). The number of b rolling and adherent leukocytes were increased 1 day after intra-articular injection of MIA, and these increases were inhibited by sivelestat (P < 0.01, P < 0.001, respectively, two-way ANOVA) and serpinA1 (P < 0.05, P < 0.001, respectively, two-way ANOVA) (n = 5–28 per time point). **P < 0.01, ***P < 0.001, and ****P < 0.0001, as compared to baseline, one-way ANOVA. Lower panel c shows representative intravital micrographs illustrating the inhibitory effect of neutrophil elastase blockade on synovial leukocyte trafficking; red arrows indicate stained leukocytes