Abstract
Objectives:Because fibroblast filamentous actin (F-actin) influences cutaneous interstitial matrix swelling pressure (5), we investigated whether F-actin in fibroblast-derived synoviocytes influences the hydraulic permeability of the transsynovial interstitial pathway. The study also tested whether F-actin in fenestrated synovial endothelium contributes to the blood-joint barrier in vivo.
Methods:The clearance of Evans blue-albumin (EVA) from plasma into the knee joint cavity was determined in joint infused with F-actin disrupting cytochalasin D (1–200 µM), latrunculin B (100 µM) or vehicle in anesthetized rabbits. The hydraulic permeability of the lining was determined as the slope relating net trans-synovial flow Qs to intra-articular pressure Pj. Synovium was examined histologically after i.v. Monastral blue to assess endothelial leakiness.
Results:EVA permeation in vivowas increased up to 25-fold by cytochalasin (p= 0.0002, ANOVA), with an EC50of 23 µM (95% confidence limits 13–43 µM). Washout quickly reversed the increase. Latrunculin had a similar effect. F-actin disruption switched Qsfrom drainage (control) to filtration into the cavity at low Pjin vivoand raised the conductance dQs/dPj by 2.13 (p= 0.001, ANOVA). Circulatory arrest abolished these effects. Monastral blue revealed numerous endothelial leaks.
Conclusions:F-actin is crucial to the barrier function of fenestrated endothelium in situ. No significant effect of synoviocyte F-actin on matrix permeability was detected.
Microcirculation(2002) 9,419–430. doi:10.1038/sj.mn.7800149