CARTILAGE PROTEOGLYCAN-INDUCED ARTHRITIS IN BALB/C MICE - ANTIBODIES THAT RECOGNIZE HUMAN AND MOUSE CARTILAGE PROTEOGLYCAN AND CAN CAUSE DEPLETION OF CARTILAGE PROTEOGLYCAN WITH LITTLE OR NO SYNOVITIS
CARTILAGE PROTEOGLYCAN-INDUCED ARTHRITIS IN BALB/C MICE - ANTIBODIES THAT RECOGNIZE HUMAN AND MOUSE CARTILAGE PROTEOGLYCAN AND CAN CAUSE DEPLETION OF CARTILAGE PROTEOGLYCAN WITH LITTLE OR NO SYNOVITIS
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DOI：
10.1002/art.1780330912
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发表时间：
1990-09-01
影响因子：
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通讯作者：
POOLE, AR
中科院分区：
文献类型：
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作者：
DAYER, E;MATHAI, L;POOLE, AR
人胎儿软骨蛋白多糖（PG）诱导BALB/c小鼠糜烂性多关节炎和脊柱炎的发展。我们检测了从免疫小鼠中分离的3种与小鼠软骨PG交叉反应的人胎儿软骨PG单克隆抗体（MAb）的性质。与含有与硫酸角蛋白反应的抗体的关节炎小鼠血清相比，MAb 202 （IgG1）仅与分布在透明质酸结合区和硫酸软骨素附着区的蛋白质相关表位反应。MAb 813 （IgG）与相同片段反应并识别出具有硫酸角蛋白免疫特性的表位。MAb 945 （IgM）仍有待进一步鉴定。将分泌MAb 202和MAb 945的杂交瘤引入辐照小鼠，导致关节软骨和生长板软骨（仅含有MAb 202）的PG丢失，甲苯胺蓝染色丢失。Mab 202未见滑膜增生，但Mab 945可见一些增生和单核细胞浸润。免疫荧光显示，这伴随着免疫球蛋白与关节软骨的结合。分泌MAb 813的杂交瘤无软骨改变，无滑膜炎，软骨无免疫球蛋白结合。这些抗体未观察到多形核白细胞浸润。这些研究表明，MAb与小鼠软骨PG反应可通过补体依赖性和补体非依赖性机制导致透明软骨中PG的耗竭。抗体可以释放PG抗原并将其暴露于免疫细胞，同时也会导致PG依赖性软骨的机械特性丧失。
Human fetal cartilage proteoglycam (PG) induces the development of an erosive polyarthritis and spondylitis in BALB/c mice. We have examined the properties of 3 monoclonal antibodies (MAb) to human fetal cartilage PG isolated from immunized mice that cross-react with mouse cartilage PG. Compared with sera from arthritic mice, which contain antibodies reactive with keratan sulfate, MAb 202 (IgG1) reacted only with a protein-related epitope that is distributed on both hyaluronic acid-binding and chondroitin sulfate-attachment regions. MAb 813 (IgG) reacted with same fragments and recognized an epitope with the immunologic characteristics of keratan sulfate. MAb 945 (IgM) remains to be further characterized. Introduction of hybridomas secreting MAb 202 and MAb 945 into irradiated mice resulted in the loss of PG from articular cartilage and from growth plate cartilage (with MAb 202 only), as revealed by a loss of staining with toluidine blue. There was no synovial hyperplasia with Mab 202, but some hyperplasia and mononuclear cell infiltration was seen with MAb 945. This was accompanied by the binding of immunoglobulins to articular cartilage, as demonstrated by immunofluorescence. The hybridoma secreting MAb 813 produced no cartilage changes or synovitis, and there was no immunoglobulin binding to cartilage. Polymorphonuclear leukocyte infiltration was never observed with these antibodies. These studies indicate that MAb reactive with mouse cartilage PG can cause the depletion of PG from hyaline cartilage by mechanisms that may be both complement dependent and complement independent. Antibodies may serve to release and expose PG antigen to immune cells, as well as causing a loss of mechanical properties of cartilage that are PG dependent.