基于TLR4 / NF-κB 信号通路探讨通痹胶囊对胶原诱导型关节炎治疗机制的研究

目的:基于TLR4/NF-κB信号通路研究通痹胶囊对胶原诱导型关节炎(CIA)的治疗机制。方法:48只SD大鼠随机分为对照组、模型组、雷公藤组(0. 01 g/kg)和通痹胶囊低(0. 075 g/kg)、中(0. 150 g/kg)、高(0. 300 g/kg)剂量组,每组8只;使用牛Ⅱ型胶原和完全弗氏佐剂(CFA)建立大鼠CIA模型;采用HE染色观察滑膜组织病理情况,ELISA检测大鼠血清中白介素1β(IL-1β)、白介素6(IL-6)和肿瘤坏死因子α(TNF-α)水平,Western blot检测滑膜组织中Toll样受体4(TLR4)、髓样分化因子88(MyD88)和核因子κB(NF-κB)蛋白表达水平。结果:与正常大鼠相比,模型大鼠关节肿胀度均显著升高,通痹胶囊治疗后关节肿胀度显著降低,模型组滑膜组织增生明显,炎症细胞浸润,关节软骨破坏,通痹胶囊治疗明显改善滑膜组织的增生,降低炎症细胞的浸润;模型组大鼠血清中IL-1β、IL-6、TNF-α水平和滑膜组织中TLR4、MyD88、NF-κB蛋白水平显著升高,通痹胶囊处理后显著降低血清中IL-1β、IL-6、TNF-α水平和滑膜组织中TLR4、MyD88、NF-κB蛋白表达;与通痹胶囊高剂量组相比,TLR4激动剂处理显著提高血清中IL-1β、IL-6、TNF-α水平和滑膜组织中TLR4、MyD88、NF-κB蛋白表达。结论:通痹胶囊可以通过抑制TLR4/NF-κB信号通路,降低炎性反应,显著改善CIA症状。     

金凤颗粒对痛风性关节炎兔关节软骨MMP-1/TIMP-1表达影响

目的:探讨金凤颗粒对痛风性关节炎兔关节软骨MMP-1/TIMP-1表达的影响,明确治疗痛风性关节炎作用机制。方法:采用乙胺丁醇、腺嘌呤联合灌胃+MSU关节腔注射法复制家兔痛风性关节炎模型。成模后,随机分为模型组,金凤颗粒高、中、低剂量组(19.6、98、4.9 g/kg),别嘌醇组(0.028 g/kg),痛风定组(0.448 g/kg),另设空白组。连续7 d给药。末次给药2 h后,取各组兔的关节软骨组织,观察其病理形态学改变;并采用免疫细胞化学技术检测其MMP-1、TIMP-1表达,计算MMP-1/TIMP-1比值。结果:金凤颗粒可明显减轻兔关节软骨的炎性细胞浸润、充血、肿胀和坏死,可显著抑制MMP-1的表达(P0.05)、促进TIMP-1的活化(P0.01),并显著降低MMP-1/TIMP-1比值(P0.05)。结论:金凤颗粒可有效抑制痛风性关节炎的病理损害,其作用机制可能与其抑制MMP-1的表达、上调TIMP-1的表达,调节MMP-1/TIMP-1平衡有关,进而发挥抗炎作用。     

白芍总苷调控NF-κB/NLRP3信号通路对急性痛风性关节炎大鼠的影响机制研究

目的：探究白芍总苷（TGP）通过调控核因子-κB(NF-κB)/含NLR家族Pyrin域蛋白3(NLRP3)信号通路对急性痛风性关节炎（AGA）大鼠炎症的影响。方法：将60只SD大鼠以每组10只随机分为对照组、AGA组、秋水仙碱组、TGP-L组、TGP-M组、TGP-H组。对照组和AGA组每天进行生理盐水灌胃，秋水仙碱组、TGP-L组、TGP-M组、TGP-H组每天分别灌胃相应药物，共7 d，除对照组外均于灌胃第5天时构建尿酸钠（MSU）诱导的AGA大鼠模型；观察各组大鼠一般情况；检测大鼠步态及关节炎症指数评价、关节肿胀程度；HE染色观察大鼠踝关节滑膜组织病理学变化；ELISA法检测大鼠关节液中炎症因子水平；Western blot检测大鼠踝关节滑膜组织NF-κB p65/NLRP3通路相关蛋白表达情况。结果：与对照组相比，AGA组大鼠关节肿胀、跛行、皮毛无光泽、精神倦怠；秋水仙碱组、TGP-L组、TGP-M组、TGP-H组大鼠相关症状均得到有效改善；与对照组相比，AGA组大鼠步态级别、关节炎症指数、关节肿胀程度、组织病理学程度、TNF-α、IL-6、IL-1β、p-NF-κB p65...     

异种脐血干细胞移植胶原性关节炎小鼠Bcl-2和Bax的表达*☆

背景：类风湿性关节炎的发生发展与滑膜细胞及淋巴细胞的增殖与凋亡不平衡密切相关,其滑膜细胞存在细胞凋亡过程的异常。 目的：观察异种、异基因双份脐血干细胞移植对Ⅱ型胶原性关节炎小鼠Bcl-2和Bax表达的影响。 方法：弗氏完全佐剂+Ⅱ型胶原诱导C57BL/6(H-2b)小鼠,建立Ⅱ型胶原性关节炎小鼠模型。小鼠二次免疫接种后第2天,模型组、正常对照组尾静脉注射生理盐水,细胞移植组将脐血造血干细胞注入小鼠尾静脉内(其中单份剂量2×106/50 g;双份剂量：每份1×106/50 g,共2×106/50 g)。甲氨喋呤阳性对照组小鼠灌胃甲氨蝶呤,每次0.017 5 g/kg,每5天1次,共6次。 结果与结论：移植后第42天全部处死动物取膝及肘以下关节组织,病理组织学显示正常对照组关节面光滑,滑膜层未见炎性细胞浸润,软骨细胞形态正常;模型组滑膜组织高度增生,大量的炎性细胞浸润,软骨面破坏;甲氨蝶呤阳性对照组、单份脐血造血干细胞移植组滑膜组织可见轻度增生,少量炎性细胞浸润,双份脐血造血干细胞移植组关节软骨表面光滑,未见破坏,有极少量炎性细胞浸润。免疫组织化学检测显示,双份脐血造血干细胞移植组Bax、Bcl-2的表达低于单份脐血造血干细胞移植治疗组(P < 0.05);与正常对照组比较,差异无显著性意义(P > 0.05)。结果说明双份脐血干细胞在一定数量及作用时间内可诱导Ⅱ型胶原性关节炎小鼠滑膜细胞凋亡,对滑膜组织损伤起保护作用。     

甘草附子汤加减方通过抑制GSDMD介导的焦亡治疗CIA大鼠的作用机制研究

目的：探讨甘草附子汤加减方（GCFZD）抑制gasdermin D (GSDMD)介导细胞焦亡途径对胶原诱导性关节炎（CIA）大鼠的治疗效果。方法：SD大鼠尾跟部注射由牛Ⅱ型胶原与弗氏佐剂混合形成的乳化剂，构建CIA大鼠模型并对其关节炎指数进行评估，将成功诱发关节炎的30只雄性SD大鼠随机分为模型组、甘草附子汤低（4 g/kg）、中（8 g/kg）和高（16 g/kg）剂量组及甲氨蝶呤（1 mg/kg）组，每组6只，连续给药30 d。测定大鼠的体重、关节炎指数和足爪肿胀指数；X线影像学观察骨质破坏和软组织厚度改变；HE染色观察脾脏和关节组织病理学改变；番红O-固绿染色观察关节软骨改变；TUNEL染色观察关节内细胞焦亡发生情况；Western blot测定TLR4、caspase-1、NLRP3和GSDMD蛋白表达；real-time PCR和ELISA测定IL-1β、IL-6和IL-10细胞因子表达。结果：与模型组相比，GCFZD治疗显著改善CIA大鼠软组织肿胀和骨质破坏，降低脾脏和胸腺指数；HE染色结果显示，GCFZD治疗减轻CIA大鼠脾脏和踝关节组织病理学改变；番红O-固绿染色结果...     

塞来昔布对膝关节炎大鼠肿瘤坏死因子α信号通路及关节滑膜细胞的影响*

目的：探究塞来昔布对膝关节炎大鼠肿瘤坏死因子α（ TNF-α）信号通路及关节滑膜细胞的影响。方法： SD大鼠随机分为模型组、假手术组和治疗组,治疗组大鼠制作膝关节炎模型后给予塞来昔布进行治疗。通过 TUNEL 法、qRT-PCR 法、CCK-8 法、免疫印迹等方法检测3 组大鼠滑膜细胞凋亡情况、TNF-α mRNA表达含量、 TNF-α 蛋白含量、关节炎指数及细胞增殖情况。结果：模型组、治疗组、假手术组关节滑膜细胞凋亡率分别为 89.38%、46.84%、13.68%。模型组与假手术组、治疗组相比较,细胞凋亡率显著升高,治疗组细胞凋亡数量多 于假手术组。假手术组、治疗组细胞增殖OD值比模型组高,差异具有统计学意义,假手术组关节滑膜细胞的增 殖数量最多,模型组关节滑膜细胞的增殖数量最少,治疗组关节滑膜细胞的增殖情况比假手术组相比明显减少。 与假手术组、治疗组比较,模型组关节滑膜细胞中TNF-α 蛋白表达水平显著上升,治疗组TNF-α 蛋白表达水平较 假手术组明显升高。与假手术组、治疗组比较,模型组TNF-α mRNA含量显著升高,治疗组TNF-α mRNA表达 量较假手术组明显升高。治疗组和模型组大鼠关节炎指数相近,随着给药时间的增加,治疗组大鼠膝关节炎情况 逐渐好转,而未服用药物的模型组大鼠病情逐渐恶化。结论：塞来昔布胶囊治疗膝关节炎大鼠效果显著,能够显 著降低TNF-α 信号通路的表达水平,改善关节滑膜细胞的凋亡情况。     

蛋白酶体抑制剂MG132 对大鼠胶原诱导性关节炎的干预机制

目的：探讨蛋白酶体抑制剂MG132对大鼠胶原诱导性关节炎（Collagen induced arthritis,CIA）的干预效果及作用机制。方法：48只雌性SD大鼠被随机分为空白对照组、CIA模型组、MG132干预模型组,每组16只CIA模型组和MG132干预模型组注射牛Ⅱ型胶原建立CIA模型大鼠,初次免疫后第21天,干预组大鼠以1 mg/kg的剂量每天1次,连续14天皮下注射MG132。建模起每周观察大鼠关节肿胀程度,计算关节炎指数（Arthritis index,AI）,第42天后称重并处死大鼠;HE染色观察关节滑膜组织的病理改变;荧光底物测定法检测滑膜组织20S蛋白酶体的活性;蛋白质印迹法（Western blot）检测大鼠关节滑膜组织NF-κB/p65、IκBα蛋白的表达情况。结果：与CIA模型组比较,MG132干预模型组大鼠关节炎指数在注射MG132后一周明显降低（P<0.05）,关节滑膜组织未见明显增生,只伴有少量炎性细胞浸润。与空白对照组大鼠比较,CIA模型组大鼠关节滑膜组织20S蛋白酶体活性增高;与CIA模型组大鼠比较,MG132皮下注射干预后关节滑膜组织20S蛋白酶体活性降低（P<0.05）。与空白对照组比较,CIA模型组大鼠关节滑膜组织高表达NF-κB/p65蛋白,其中胞核NF-κB/p65表达增高更为明显（P<0.01）,注射蛋白酶体抑制剂MG132干预后,其滑膜组织胞浆及胞核NF-κB/p65蛋白表达均显著减少（P<0.01）。与空白对照组比较,CIA模型组大鼠关节滑膜低表达IκBα蛋白（P<0.01）,注射MG132干预后关节滑膜IκBα蛋白表达显著增多（P<0.01）。结论：大鼠CIA体内实验显示,蛋白酶体抑制剂MG132经皮下注射可明显改善大鼠关节炎症状,其作用机制可能与MG132降低大鼠CIA关节滑膜组织20S蛋白酶体活性,减少其底物蛋白IκBα的表达,从而抑制NF-κB活性有关。     

雷公藤多苷抑制二肽肽酶I 活性及其调节机制的研究

目的:二肽肽酶I(DPPI)是一种溶酶体半胱氨酸蛋白酶,高表达于颗粒免疫细胞包括肥大细胞,有激活炎症介质丝氨酸蛋白酶的功能。本研究用胶原诱导类风湿关节炎(Collagen-induced arthritis,CIA)大鼠模型,探讨雷公藤多苷对DPPI 的作用以揭示其治疗类风湿的药理机制。方法:Wistar 大鼠随机分为正常组、模型组和雷公藤多苷治疗组(低剂量组2.5 mg/100 g 体重,高剂量组5 mg/100 g 体重);用牛域型胶原加完全弗氏佐剂诱导大鼠类风湿关节炎,两次免疫后第12 天开始灌胃给药,连续2 周后处死,收集血液和滑膜。关节切片HE 染色和细胞计数,荧光底物法检测DPPI 在大鼠血清和滑膜中的表达和活性,明胶酶谱法检测滑膜液中MMP-2/9 表达水平,BCA 法测定样品总蛋白含量。结果:和模型组相比,雷公藤多苷能降低CIA 大鼠关节滑膜组织中肥大细胞的数量,并抑制滑膜液和血清DPPI 的活性;滑膜总蛋白和MMP-2/9 活性也有所降低。结论:雷公藤多苷对DPPI 活性的抑制作用可能是其治疗类风湿药理学机制之一。     

骨性关节炎模型大鼠关节软骨变化及透骨消痛胶囊干预的作用

背景:透骨消痛胶囊是治疗骨性关节炎的临床验方,作用机制尚未完全阐明。尿激酶型纤溶酶原激活系统参与关节软骨的细胞外基质降解及关节滑膜增生,在骨性关节炎的病理过程中起着重要作用。目的:观察透骨消痛胶囊对膝骨性关节炎模型大鼠软骨中尿激酶型纤溶酶原激活系统的影响。方法:SD大鼠144只,随机取120只采用关节腔注射木瓜蛋白酶复制大鼠膝骨性关节炎模型,并随机分为模型组、壮骨关节丸组[1.2 g/(kg·d)]、透骨消痛胶囊低剂量组[0.092 g/(kg·d)]、透骨消痛胶囊中剂量组[0.184 g/(kg·d)]和透骨消痛胶囊高剂量组[0.368 g/(kg·d)],每组24只,每2周为1个疗程,中间休息2 d,共4个疗程。另取24只正常大鼠为空白组。每2个疗程后,处死一批实验动物,苏木精-伊红染色观察软骨组织病理改变;免疫组织化学反应观察尿激酶型纤溶酶原激活剂、尿激酶型纤溶酶原激活剂受体、纤溶酶原激活物抑制因子阳性表达情况;Western blot检测尿激酶型纤溶酶原激活剂、尿激酶型纤溶酶原激活剂受体、纤溶酶原激活物抑制因子蛋白表达情况。结果与结论:透骨消痛胶囊组和壮骨关节丸组的骨性关节炎大鼠关节软骨Mankin’s评分较模型组明显降低(P0.01),具有时间依赖;免疫组织化学反应显示,透骨消痛胶囊组和壮骨关节丸组尿激酶型纤溶酶原激活剂、尿激酶型纤溶酶原激活剂受体的阳性率明显降低,而纤溶酶原激活物抑制因子明显升高,具有时间依赖。Western blot检测结果与免疫组织化学具有相同的趋势。提示透骨消痛胶囊可能通过调控尿激酶型纤溶酶原激活剂系统对骨性关节炎发挥防治作用。     

基于PI3K/AKT/FoxO1信号通路探究补阳还五汤对痛风模型大鼠滑膜组织细胞凋亡及炎症反应的影响

目的 基于磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B(AKT)/叉头框转录因子O亚族1(FoxO1)信号通路探究补阳还五汤对痛风模型大鼠滑膜组织细胞凋亡及炎症反应的影响。方法 大鼠分为对照组（灌胃生理盐水）、痛风组（建模+灌胃生理盐水）、西药组（建模+灌胃20 mg/kg苯溴马隆）、补阳还五汤低、高剂量组（建模+灌胃6.5、26.0 g/kg补阳还五汤）和通路激活组（建模+灌胃26.0 g/kg补阳还五汤+腹腔注射0.02 mg/kg PI3K活化物（740Y-P））。测量大鼠关节肿胀度,测定血清尿酸、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)水平,对滑膜组织进行HE染色及TUNEL检测,测定滑膜组织中p-PI3K/PI3K、pAKT/AKT、p-FoxO1/FoxO1、Caspase-3蛋白表达水平。结果 与对照组相比,痛风组大鼠关节肿胀度及血清尿酸、TNF-α、IL-1β水平及滑膜组织中p-PI3K/PI3K、p-AKT/AKT、p-FoxO1/FoxO1蛋白表达水平显著升高（P<0.05）,滑膜组织中细胞凋亡率及Caspase-3蛋白表达水平显著降低（P...     

The synovitis of acute gouty arthritis. A light and electron microscopic study

The synovium participates in the inflammatory process of acute gouty arthritis with intense polymorphonuclear leukocyte infiltration, but many chronic inflammatory cells are also seen even during the acute attack. Crystals in the synovial membrane were found in three patients and then only in well defined tophi. Tophus structure was consistent with crystal deposition in a collagen and amorphous matrix with little adjacent inflammatory reaction. Microtophi were superficial and thinly encapsulated, suggesting that crystals from these tophi might easily rupture into the joint space to initiate the inflammatory reaction. Crystals were seen in detached lining cells and other macrophages as well as in polymorphonuclear leukocytes in the synovial fluid. Clinically satisfactory doses of colchicine produced no detectable morphologic changes in microtubules or other structures.     

Quantitative histological analysis of antigen-induced arthritis in the rabbit

Antigen-induced arthritis in the rabbit (AIAR) provides the closest experimental equivalent to human rheumatoid arthritis in terms of infiltration of synovial tissue by lymphoid cells. A method is described for quantitative histological analysis of AIAR. Measurements of total cell numbers, lymphocyte and polymorphonuclear leucocyte infiltration, and thickness of infiltrated synovium were obtained for ranges of antigen dosage and duration of arthritis. The method has been devised as part of a system for the analysis of joint swelling, synovial fluid biochemistry and cytology, cartilage proteoglycan chemistry and synovial histology on the same specimen.     

Quantitative histological analysis of antigen-induced arthritis in the rabbit.

Antigen-induced arthritis in the rabbit (AIAR) provides the closest experimental equivalent to human rheumatoid arthritis in terms of infiltration of synovial tissue by lymphoid cells. A method is described for quantitative histological analysis of AIAR. Measurements of total cell numbers, lymphocyte and polymorphonuclear leucocyte infiltration, and thickness of infiltrated synovium were obtained for ranges of antigen dosage and duration of arthritis. The method has been devised as part of a system for the analysis of joint swelling, synovial fluid biochemistry and cytology, cartilage proteoglycan chemistry and synovial histology on the same specimen.     

Immunochemical and Ultrastructural Characterization of Serum Proteins Associated with Monosodium Urate Crystals (MSU) in Synovial Fluid Cells from Patients with Gout

Immunoelectron microscopic (IEM) analysis of the surface coats of intracellular and extracellular monosodium urate (MSU) crystals in synovial fluid (SF) in gouty arthritis was performed using the ferritin-bridge method. Cells from patients with acute gout were fixed in 1% glutaraldehyde containing 0.05% saponin to permeabilize membranes for access of immunochemicals to intracellular antigens. Intracellular MSU crystals were observed in phagosomes of greater than 75% of both polymorphonuclear (PMNs) and mononuclear cells. Coating of crystals with IgG was more prominent than with IgM or IgA. Other proteins such as C3, and fibrinogen were also found to a lesser extent. Albumin was not detected in appreciable amounts on MSU crystals. Extracellular crystals also showed IgG to be bound more prominently than other proteins. The various proteins, shown here for the first time to be clearly associated with intracellular crystals by EM, and other materials associated with MSU crystals May-Jun influence the phlogistic properties of these crystals.     

Anti-inflammatory effects of intravenous methotrexate associated with lipid nanoemulsions on antigen-induced arthritis

OBJECTIVE:To test the hypothesis that intravenous use of methotrexate associated with lipid nanoemulsions can achieve superior anti-inflammatory effects in the joints of rabbits with antigen-induced arthritis compared with commercial methotrexate.METHODS:Arthritis was induced in New Zealand rabbits sensitized with methylated bovine serum albumin and subsequently intra-articularly injected with the antigen. A nanoemulsion of methotrexate labeled with ³H-cholesteryl ether (4 mg/kg methotrexate) was then intravenously injected into four rabbits to determine the plasma decaying curves and the biodistribution of the methotrexate nanoemulsion by radioactive counting. Additionally, the pharmacokinetics of the methotrexate nanoemulsion were determined by high-pressure liquid chromatography. Twenty-four hours after arthritis induction, the animals were allocated into three groups, with intravenous injection with saline solution (n=9), methotrexate nanoemulsion (0.5 µmol/kg methotrexate, n=7), or commercial methotrexate (0.5 µmol/kg, n=4). The rabbits were sacrificed 24 h afterward. Synovial fluid was then collected for protein leakage and cell content analyses and synovial membranes were collected for histopathological analysis.RESULTS:The methotrexate nanoemulsion was taken up mainly by the liver and the uptake by arthritic joints was two-fold greater than that by control joints. The methotrexate nanoemulsion treatment reduced leukocyte influx into the synovial fluid by nearly 65%; in particular, mononuclear and polymorphonuclear cells were reduced by 47 and 72%, respectively. In contrast, cell influx was unaffected following treatment with commercial methotrexate. Protein leakage into the arthritic knees of the rabbits was also more limited following methotrexate nanoemulsion treatment than following commercial methotrexate treatment.CONCLUSIONS:The intravenous methotrexate nanoemulsion showed anti-inflammatory effects on the synovia of arthritic joints that were clearly superior to the effects of a commercial methotrexate preparation. This result is conceivably due to greater methotrexate uptake by the joints when the drug is associated with a nanoemulsion.     

Chemokines and leukocyte trafficking in rheumatoid arthritis.

Leukocyte infiltration into the joint space and tissues is an essential component of the pathogenesis of rheumatoid arthritis (RA). In this review, we will summarize the current understanding of the mechanisms of leukocyte trafficking into the synovium, focusing on the role of adhesion molecules, chemokines, and chemokine receptors in synovial autoimmune inflammation. The process by which a circulating leukocyte decides to migrate into the synovium is highly regulated and involves the capture, firm adhesion, and transmigration of cells across the endothelial monolayer. Adhesion molecules and chemokine signals function in concert to mediate this process and to organize leukocytes into distinct structures within the synovium. Chemokines play a key regulatory role in organ-specific leukocyte trafficking and activation by affecting integrin activation, chemotaxis, effector cell function, and cell survival. Consequently, chemokines, their receptors, and downstream signal transduction molecules are attractive therapeutic targets for RA.     

Progression of Articular Destruction and the Production of Tumour Necrosis Factor-α in Antigen-Induced Arthritis in Rabbits

We examined the progression of articular destruction and the production of tumour necrosis factor-α (TNF-α) in antigen-induced arthritis (AIA) in rabbits, i.e. flare-ups of inflammation induced by repeated intra-articular injections (single, twice and three times) of antigen. A marked progression of articular destruction and an infiltration of inflammatory cells in the synovium were observed with the increase in the number of antigen injections. An immunohistochemical analysis of the synovial lesions following three injections of antigen revealed that the lymphoid follicles consisted mainly of CD4⁺ T cells and IgG/IgM⁺ B cells. There were marked infiltrations of IgG⁺ plasma cells around the lymphoid follicles. In contrast, the production of TNF-α in the synovial fluid and the erythrocyte sedimentation rate (ESR), which is a marker of systemic inflammatory activity in rheumatoid arthritis, peaked at 6 h and 24 h, respectively, following the last injection of antigen. These values were also greater following the repeated injections of antigen compared with the single injection. The TNF-α was produced markedly in the joints at the onset of the flare-ups of arthritis following the repeated injections of antigen, and the elevation of the ESR and an acceleration of the inflammatory response in the synovium were observed with a concomitant progression of severe articular destruction, suggesting that the marked production of TNF-α at the time of flare-ups may be involved in the exacerbation of AIA in rabbits.     

Immunopathological changes in rheumatoid arthritis and other joint diseases.

A comparative study of the distribution of immunoglobulins G, M, and A and C3 in the synovium and inside synovial fluid leucocytes and of the relative levels of IgG, IgM, AND C3 in paired samples of serum and synovial fluid from both seropositive and seronegative patients with rheumatoid arthritis and other types of non-infective synovitis shows that although there is no distinctive immunopathological feature of rheumatoid arthritis, the incidence of immune complexes containing IgG and IgM with and without detectable C3 in the affected synovium or inside synovial fluid granulocytes is higher in rheumatoid arthritis and especially so in seropositive cases. The mean level of C3 in synovial fluid from patients with rheumatoid arthritis is lower than that from the group without rheumatoid arthritis. In contrast to previous reports, extracellular clumps of IgA could be detected in the affected synovium of a number of affected patients. Aggretated human IgG could be bound by some of the synovial biopsies and synovial fluid leucocytes from both seropositive and seronegative rheumatoid arthritis patients. Antinuclear factor and rheumatoid factor could be detected in the synovial fluid but not in the serum of several patients suggesting either selective sequestration or local synthesis of antinuclear and rheumatoid factors in the affected joints.     

Cellular Fibronectin in Rheumatoid Synovium and Synovial Fluid: a Possible Factor Contributing to Lymphocytic Infiltration

Mouse monoclonal antibodies against ED sequence-containing cellular fibronectin (cFn) were used to show that Fn in the inflamed synovium is distinct from the major form of plasma Fn (pFn). An accumulation of cFn was seen at sites of hyperplasia of the rheumatoid synovial membrane and in the walls of small vessels in the synovium by immunofluorescence microscopy. cFn was also found in rheumatoid synovial fluid by immunoblotting. Approximately one-fifth of the T lymphocytes from rheumatoid synovial fluid bound to Fn. The binding of synovial fluid T cells was always higher than that from peripheral blood. These results have two implications. On the one hand, the cellular type of Fn may be an indicator of synovial inflammation. On the other hand, the deposition of Fn may be a factor contributing to the infiltration of mononuclear cells into the synovium.