Influence of actin cytoskeleton on intra-articular and interstitial fluid pressures in synovial joints

Fibroblast microfilamentous actin (F-actin) influences interstitial fluid pressure via linkages to collagen in rat skin (Berg et al., 2001). The present aims were to determine whether the actin cytoskeleton of synovial endothelium, fibroblasts, and synoviocytes influences in vivo (i) fluid exchange between a joint cavity and synovial microcirculation and (ii) extracellular fluid pressures in joints. Rabbit knee joints were treated intra-articularly with the F-actin disrupting drugs cytochalasin D and latrunculin B while joint fluid pressure P(j) was recorded. In joints injected with small volumes of control solution, P(j) fell with time (-0.05 +/- 0.01 cm H2O x min(-1), mean +/- SEM, n = 9, equivalent drainage rate 3.9 microl x min(-1)). Cytochalasin or latrunculin reversed this in approximately 4 min in vivo; P(j) increased with time, e.g., +0.12 +/- 0.04 cm H2O x min(-1) at 200 microM cytochalasin (equivalent filtration rate into joint 6.6-12.5 microl x min(-1), n = 4), with a cytochalasin EC50 of 45 microM. Plasma gamma-globulin clearance into the joint cavity was also increased. Post mortem, cytochalasin did not reverse dP(j)/dt and had no more effect on P(j) than did control solution. Also, when synovial interstitial fluid pressures were measured by servonull micropipette post mortem (control -0.95 +/- 0.37 cmH2O, n = 18) cytochalasin had no significant effect on interstitial pressure over 60 min, even at 1 mM. It was concluded that synovial endothelial F-actin has an important role in the normal synovial microvascular resistance to fluid filtration and plasma gamma-globulin permeation and is thus a potential link between pro-inflammatory mediators and arthritic joint effusions. The results provided no support for the hypothesis that synoviocyte F-actin influences the swelling tendency of synovial matrix and hence extracellular fluid pressures, in contrast to the findings of Berg et al. (2001) in rat dermis.