CA-4-P induces an increase in endothelial monolayer permeability to dextrans.

(A) Confluent endothelial monolayers grown on transwell filters were treated with vehicle control (○), CA-4-P (15 minutes, 1 μM) (●), C3 exoenzyme (24 hours, 10 μg/mL) followed by CA-4-P (15 minutes, 1 μM) (▴), and Y-27632 (30 minutes, 10 μM) followed by CA-4-P (▪). Data for inhibitors alone are not plotted and were not significantly different from inhibitors plus CA-4-P. Medium was replaced with FITC-dextran, and its passage through the filters was monitored at time intervals for 1 hour. In inset, passage of dextran through parallel cultures exposed to EGTA (5 mM, 15 minutes) (▵) is compared with vehicle (○) and CA-4-P (●). (B) Values taken at 60-minute time point in panel A are expressed as the percentage of fluorescent dextran passing through monolayers exposed to EGTA (see inset, 60-minute time point). Preincubation with HA1077 was for 30 minutes at 10 μM. Inhibitors were followed by either 15 minutes of vehicle control or 15 minutes of 1 μM CA-4-P. Mean values ± SEM were obtained from 3 separate filters from one of 3 representative experiments. *P < .05 for CA-4-P compared to vehicle or for inhibitors + CA-4-P compared to CA-4-P vehicle.