Electrical charge of the antigen determines intraarticular antigen handling and chronicity of arthritis in mice.
Electrical charge of the antigen determines intraarticular antigen handling and chronicity of arthritis in mice.
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DOI：
10.1172/jci111604
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发表时间：
1984-11
期刊：
影响因子：
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通讯作者：
W. B. van den Berg;L. van de Putte;W. A. Zwarts;L. Joosten
中科院分区：
文献类型：
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作者：
W. B. van den Berg;L. van de Putte;W. A. Zwarts;L. Joosten
我们研究了抗原电荷对关节内抗原处理的影响以及对抗原诱导慢性关节炎的能力的影响。使用了三种不同的抗原：阴离子天然牛血清白蛋白（BSA）和通过甲基化（mBSA）或酰胺化（aBSA）制成阳离子（pI 8.5）的电荷改性BSA。将125I标记的抗原注射到非免疫小鼠和用抗原在弗氏完全佐剂中免疫的小鼠的膝关节中。在免疫和非免疫小鼠中，与天然BSA相比，阳离子抗原mBSA和aBSA的关节内抗原保留显著增加。体外研究表明阳离子抗原与关节组织结合的静电特性，并证实了体内发现的抗原保留的巨大差异。与抗体介导的捕获天然BSA相比，100倍量的阳离子抗原可以结合到关节的非软骨胶原组织，并且对于透明关节软骨，这种差异甚至更大。在免疫小鼠中，慢性关节炎仅在关节内注射阳离子抗原后发生。这一现象显然与mBSA和aBSA的保留增加有关，因为所用的三种抗原的迟发型超敏反应和体液免疫相当。我们的数据表明，抗原电荷是一个重要的决定因素的抗原处理的关节，此外，支持的概念，即慢性关节炎的发展取决于保留在关节中的抗原的量。
We studied the influence of antigenic charge on the handling of intraarticular antigen by the joint and on the ability of the antigen to induce chronic arthritis. Three different antigens were used: anionic native bovine serum albumin (BSA), and charge modified BSA made cationic (pI 8.5) either by methylation (mBSA), or amidation (aBSA). 125I-labeled antigen was injected into the knee joints of nonimmune mice and of mice immunized with antigen in Freund's complete adjuvant. Intraarticular antigen retention of the cationic antigens mBSA and aBSA was significantly increased compared with native BSA, both in immune and non-immune mice. In vitro studies indicated the electrostatic character of the binding of the cationic antigens to joint tissues and confirmed the large difference in antigen retention of the antigens found in vivo. A 100-fold amount of cationic antigen could be bound to non-cartilaginous collagenous tissue of the joint compared with antibody-mediated trapping of native BSA, and for hyaline articular cartilage, this difference was even greater. In immunized mice, chronic arthritis only developed after intraarticular injection of the cationic antigens. This phenomenon was apparently related to increased retention of mBSA and aBSA compared with BSA, since delayed hypersensitivity and humoral immunity were comparable for the three antigens used. Our data indicate that antigenic charge is an important determinant of antigen handling by the joint and, in addition, support the concept that the development of chronic arthritis depends on the amount of antigen retained in the joint.