Cationization of catalase, peroxidase, and superoxide dismutase. Effect of improved intraarticular retention on experimental arthritis in mice.
Cationization of catalase, peroxidase, and superoxide dismutase. Effect of improved intraarticular retention on experimental arthritis in mice.
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DOI：
10.1172/jci111946
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发表时间：
1985-07
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影响因子：
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通讯作者：
J. Schalkwijk;Wim;B. V. den;Berg;Levinus B. A. van de;Putte;Leo;A. B. Joosten;Liduine;van den Bersselaar
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文献类型：
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作者：
J. Schalkwijk;Wim;B. V. den;Berg;Levinus B. A. van de;Putte;Leo;A. B. Joosten;Liduine;van den Bersselaar
一些酶和其他蛋白质通过与聚赖氨酸偶联或屏蔽阴离子位点而成为阳离子。这些阳离子蛋白，均具有大于8.5的等电点，当注射到小鼠膝关节时，在关节结构中表现出良好的保留。放射自显影和组织化学显示，阳离子形式的过氧化氢酶、超氧化物歧化酶和辣根过氧化物酶在滑膜和软骨组织中被牢固地保留。因此，与天然酶相比，这些酶在关节中的半衰期明显延长。用抗原诱导的关节炎和酶蛋白诱导的关节炎在小鼠身上测试了天然酶及其阳离子衍生物的抗炎特性。研究发现，注射阳离子过氧化氢酶或过氧化物酶可显著抑制两种关节炎中炎症反应的某些参数，这是通过99m高锝酸盐摄取和125i标记白蛋白渗漏来测量的。天然过氧化氢酶和过氧化物酶作用较小，或根本不起作用。阳离子超氧化物歧化酶或阳离子非酶蛋白对炎症无抑制作用。过氧化氢酶和过氧化物酶对两种不同类型的炎症（免疫性关节炎和非免疫性关节炎）的抑制表明，消除过氧化物有助于抑制炎症反应。我们假设阳离子酶为研究炎症机制提供了可能性，此外，从治疗的角度来看，阳离子酶可能很有趣。
Several enzymes and other proteins were made cationic either by coupling to polylysine or by shielding of anionic sites. These cationic proteins, all having an isoelectric point greater than 8.5 exhibited excellent retention in articular structures when injected in mouse knee joints. Autoradiography and histochemistry showed that cationic forms of catalase, superoxide dismutase, and horseradish peroxidase were firmly retained by synovial and cartilaginous tissues. The half-life of these enzymes in the joint is thus significantly extended compared with native enzymes. The native enzymes and their cationic derivatives were tested for antiinflammatory properties in mice, using antigen-induced arthritis and zymosan-induced arthritis. It was found that injection of cationic catalase or peroxidase induced a marked suppression of some parameters of the inflammatory response in both types of arthritis, as measured by 99m technetium pertechnetate uptake and leakage of 125I-labeled albumin. Native catalase and peroxidase were less, or not at all effective. Cationic superoxide dismutase or cationic nonenzyme proteins did not suppress inflammation. The observed suppression of two different types of inflammation (an immune and a nonimmune arthritis) by catalase and peroxidase suggests that elimination of peroxides contributes to the suppression of an inflammatory response. We would hypothesize that cationic enzymes offer the possibility for investigating the mechanisms of inflammation and, in addition, might be interesting from a therapeutical point of view.