A. Poli et al., Influence of actin cytoskeleton on intra-articular and interstitial fluid pressures in synovial joints, MICROVASC R, 62(3), 2001, pp. 293-305
Fibroblast microfilamentous actin (F-actin) influences interstitial fluid p
ressure via linkages to collagen in rat skin (Berg et al., 2001). The prese
nt aims were to determine whether the actin cytoskeleton of synovial endoth
elium, fibroblasts, and synoviocytes influences in vivo W fluid exchange be
tween a joint cavity and synovial microcirculation and (ii) extracellular f
luid pressures in joints. Rabbit knee joints were treated intra-articularly
with the F-actin disrupting drugs cytochalasin D and latrunculin B while j
oint fluid pressure P-j was recorded. In joints injected with small volumes
of control solution, Pj fell with time (-0.05 +/- 0.01 cm H2O min(-1), mea
n +/- SEM, n = 9, equivalent drainage rate 3.9 mul min(-1)). Cytochalasin o
r latrunculin reversed this in similar to4 min in vivo; P-j increased with
time, e.g., +0.12 +/- 0.04 cm H2O min(-1) at 200 muM cytochalasin (equivale
nt filtration rate into joint 6.6-12.5 mul min(-1), n = 4), with a cytochal
asin EC50 of 43 muM. 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 i
nterstitial fluid pressures were measured by servonull micropipette post mo
rtem (control -0.95 +/- 0.37 cm H2O, n = 18) cytochalasin had no significan
t effect on interstitial pressure over 60 min, even at 1 mM. It was conclud
ed that synovial endothelial F-actin has an important role in the normal sy
novial microvascular resistance to fluid filtration and plasma. gamma -glob
ulin permeation and is thus a potential link between pro-inflammatory media
tors and arthritic joint effusions. The results provided no support for the
hypothesis that synoviocyte F-actin influences the swelling tendency of sy
novial matrix and hence extracellular fluid pressures, in contrast to the f
indings of Berg et al. (2001) in rat dermis. (C) 2001 Academic Press.