Camerlain M, McCarty D J, Silcox D C, Jung A
J Clin Invest. 1975 Jun;55(6):1373-81. doi: 10.1172/JCI108056.
Recent studies have shown elevated inorganic pyrophosphate (PPi) levels in most knee joint fluid supernates from patients with pseudogout (PG) or osteoarthritis (OA) and more modestly elevated levels in some supernates from patients with gout or rheumatoid arthritis (RA) relative to PPi levels found in the venous blood plasma of normal or arthritic subjects. We measured the intraarticular PPi pool and its rate of turnover to better understand the significance of the joint fluid-plasma PPi gradient. Preliminary studies in rabbits showed that (32-P)PPi passed from joint space to blood and vice versa without detectable hydrolysis. Incubation of natural or synthetic calcium pyrophosphate dihydrate (CPPD) microcrystals with synovial fluid in vitro in the presence of (32P)PPi tracer showed no change in PPi specific activity in the supernate over a 19-h period so that exchange of PPi in solution with that in CPPD microcrystals could be ignored. Clearance rates of (32P)PPi and of (33P)Pi, as determined by serially sampling the catheterized knee joints of volunteers with various types of arthritis over a 3-h period, were nearly identical. The (32P)PPi/(32P)Pi was determined in each sample. A mixture of a large excess of cold PPi did not influence the clearance rate of either nuclide. The quantity of PPi turned over per hous was calculated from the pool size as determined by isotope dilution and the turnover rate. The residual joint fluid nuclide was shown to be (32P)PPi. The PPi pool was generally smaller and the rate of turnover was greater in clinically inflamed joints. The mean plus or minus SEM pool size (mu-moles) and turnover rate (percent/hour) in PG knees was 0.23 plus or minus 0.07 and 117 plus or minus 11.9, hydrolysis rate (%/h) to Pi was 27.7 plus or minus 13.2; in OA knees: 0.45 plus or minus 0.26 and 72 plus or minus 9.2, hydrolysis 6.9 plus or minus 0.9; in gouty knees: 0.8 plus or minus 0.41 and 50 plus or minus 11.6, hydrolysis 9.8 plus or minus 2.8; and in RA knees: 0.14 plus or minus 0.14 and 114 plus or minus 35.8, hydrolysis 236 plus or minus 116. PPi turnover (mumoles/hour) correlated with the degree of OA change present in the joint as graded by radiologic criteria irrespective of the clinical diagnosis. Mean PPi turnover in joints with advanced OA was greater than in those with mild or moderate changes (P smaller than 0.001), but the mild and moderate groups showed no significant difference. We conclude that synovial PPi turnover and elevated PPi fluid concentrations are not specific for PG patients, and that these factors alone cannot be the only determinants of CPPD crystal deposition.
最近的研究表明，与正常或关节炎患者静脉血浆中的无机焦磷酸（PPi）水平相比，假性痛风（PG）或骨关节炎（OA）患者的大多数膝关节液上清液中PPi水平升高，痛风或类风湿关节炎（RA）患者的一些上清液中PPi水平有适度升高。我们测量了关节内PPi池及其周转率，以更好地理解关节液 - 血浆PPi梯度的意义。对兔子的初步研究表明，（32 - P）PPi在关节间隙和血液之间相互传递，且未检测到水解。在（32P）PPi示踪剂存在的情况下，将天然或合成的二水焦磷酸钙（CPPD）微晶与滑液在体外孵育19小时，上清液中PPi比活性没有变化，因此可以忽略溶液中的PPi与CPPD微晶中的PPi之间的交换。通过在3小时内对患有各种类型关节炎的志愿者的插管膝关节进行连续采样来测定（32P）PPi和（33P）Pi的清除率，二者几乎相同。在每个样本中测定（32P）PPi/（32P）Pi。大量过量冷PPi的混合物不影响任何一种核素的清除率。根据同位素稀释法测定的池大小和周转率计算每小时周转的PPi量。残留的关节液核素显示为（32P）PPi。临床上发炎的关节中，PPi池通常较小，周转率较高。PG膝关节中，平均±标准误的池大小（微摩尔）和周转率（%/小时）分别为0.23±0.07和117±11.9，水解为Pi的速率（%/小时）为27.7±13.2；OA膝关节中：0.45±0.26和72±9.2，水解6.9±0.9；痛风性膝关节中：0.8±0.41和50±11.6，水解9.8±2.8；RA膝关节中：0.14±0.14和114±35.8，水解236±116。PPi周转率（微摩尔/小时）与根据放射学标准分级的关节中OA变化程度相关，与临床诊断无关。晚期OA关节的平均PPi周转率高于轻度或中度变化的关节（P小于0.001），但轻度和中度组之间无显著差异。我们得出结论，滑膜PPi周转率和升高的PPi液浓度并非PG患者所特有，而且这些因素本身不能是CPPD晶体沉积的唯一决定因素。
