Contribution of F-actin to barrier properties of the blood-joint pathway.
OBJECTIVE
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 trans-synovial 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 microM), latrunculin B (100 microM) or vehicle in anesthetized rabbits. The hydraulic permeability of the lining was determined as the slope relating net trans-synovial flow Q(s) to intra-articular pressure P(j). Synovium was examined histologically after i.v. Monastral blue to assess endothelial leakiness.


RESULTS
EVA permeation in vivo was increased up to 25-fold by cytochalasin (p = 0.0002, ANOVA), with an EC(50) of 23 microM (95% confidence limits 13-43 microM). Washout quickly reversed the increase. Latrunculin had a similar effect. F-actin disruption switched Q(s) from drainage (control) to filtration into the cavity at low P(j) in vivo and raised the conductance Q(s)/dP(j) 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.
Poli
A
A
Department of Physiology, St. George's Hospital Medical School, London, UK.
Coleman
P J
PJ
Mason
R M
RM
Levick
J R
JR
D000199:Actins / Q000502:physiology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D015638:Cytochalasin D / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000648:ultrastructure; D005070:Evans Blue / Q000493:pharmacokinetics; D005110:Extracellular Space; D007719:Knee Joint / Q000098:blood supply* / Q000648:ultrastructure; D008833:Microcirculation; D011817:Rabbits; D013582:Synovial Fluid; D013583:Synovial Membrane / Q000166:cytology / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D013844:Thiazoles; D053778:Thiazolidines; D015638:Cytochalasin D; D005070:Evans Blue; C037068:latrunculin B