Blockade of IL-8-induced migration by exposure to rhAPC. (A) Effect of rhAPC on neutrophil chemotaxis in vitro. Neutrophils isolated from blood of healthy volunteers were exposed to rhAPC (♦, 10-4 g/mL; ^*, 10^-6 g/mL; ▴, 10^-8 g/mL; •, 10^-10 g/mL) or left untreated (□) for 20 minutes. Plot depicts mean chemotaxis index (n = 5) of IL-8-induced migration (1 nM gradient) over a 2-hour period in a modified Boyden chamber system. Pretreatment with rhAPC resulted in a significant reduction in IL-8-induced migration over time for all concentrations tested when compared with untreated cells (10^-4 g/mL, P < .0001; 10^-6 g/mL, P < .0001; 10^-8 g/mL, P < .0001; 10^-10 g/mL, P = .01; by 2-way ANOVA). (B) Effect of rhAPC on neutrophil chemotaxis ex vivo. Neutrophils isolated 16 hours after endobronchial LPS-instillation from BALF of volunteers who received rhAPC (•) demonstrate a significant decrease in IL-8-induced migration over a 1-hour period compared with placebo-treated volunteers (○). Mean index ± SEM (n = 3 for rhAPC-treated group, n = 4 for untreated group), P = .012 by 2-way ANOVA.