Poli A, Scott D, Bertin K, Miserocchi G, Mason R M, Levick J R
Department of Physiology, St. George's Hospital Medical School, London, SW17 ORE, United Kingdom.
Microvasc Res. 2001 Nov;62(3):293-305. doi: 10.1006/mvre.2001.2349.
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.
成纤维细胞微丝肌动蛋白（F-肌动蛋白）通过与大鼠皮肤中的胶原蛋白连接来影响组织液压力（伯格等人，2001年）。本研究旨在确定滑膜内皮细胞、成纤维细胞和滑膜细胞的肌动蛋白细胞骨架是否在体内影响（i）关节腔与滑膜微循环之间的液体交换以及（ii）关节中的细胞外液压力。给兔膝关节关节腔内注射破坏F-肌动蛋白的药物细胞松弛素D和拉春库林B，同时记录关节液压力P(j)。在注射少量对照溶液的关节中，P(j)随时间下降（-0.05±0.01 cm H2O×min(-1)，平均值±标准误，n = 9，等效引流速率3.9 μl×min(-1)）。细胞松弛素或拉春库林在体内约4分钟内逆转了这种情况；P(j)随时间增加，例如，在200 μM细胞松弛素时为+0.12±0.04 cm H2O×min(-1)（等效进入关节的滤过速率6.6 - 12.5 μl×min(-1)，n = 4），细胞松弛素的半数有效浓度（EC50）为45 μM。血浆γ-球蛋白向关节腔的清除率也增加。死后，细胞松弛素并未逆转dP(j)/dt，对P(j)的影响也不大于对照溶液。此外，当死后用伺服零位微量移液器测量滑膜组织液压力时（对照为-0.95±0.37 cmH2O，n = 18），即使在1 mM时，细胞松弛素在60分钟内对组织液压力也没有显著影响。得出的结论为，滑膜内皮F-肌动蛋白在滑膜微血管对液体滤过和血浆γ-球蛋白渗透的正常抵抗中起重要作用，因此是促炎介质与关节炎关节积液之间的潜在联系。与伯格等人（2001年）在大鼠真皮中的发现相反，结果不支持滑膜细胞F-肌动蛋白影响滑膜基质肿胀趋势进而影响细胞外液压力这一假说。
