Turkall R M, Warr G A, Tsan M F
Agents Actions. 1982 Oct;12(4):489-98. doi: 10.1007/BF01965932.
It has been shown that gold accumulates in macrophages. In vitro studies have also shown that long-term anti-inflammatory and immuno-regulatory effects on these cells may be responsible for the effectiveness of gold in the treatment of rheumatoid arthritis. However, the relevance of this information to the in vivo circumstance is largely untested. In this study, the effect of gold sodium thiomalate (AuTM) on rat alveolar macrophage (AM) lysosomal enzymes, bacterial killing, and metabolic activities associated with phagocytosis were assessed after in vivo administration. The activities of beta-glucuronidase, acid phosphatase, and lysozyme were inhibited 1 day following a single AuTM injection (50 mg/kg, subcutaneous). However, lysozyme returned to normal, while the activities of beta-glucuronidase and acid phosphatase were elevated from 4 to 12 days thereafter. When AuTM was administered weekly for 8 weeks, the activities of acid phosphatase and beta-glucuronidase were elevated throughout, while lysozyme was largely unaffected. The increased lysosomal enzyme activities were not due to contamination of polymorphonuclear leukocytes. These long-term effects of AuTm on enzyme activity were in marked contrast to its in vitro effect which inhibited the activities of beta-glucuronidase and acid phosphatase. No effect of AuTM administration on the release of beta-glucuronidase upon phagocytosis of opsonized zymosan was observed. At 1 day following a single AuTM injection or 3 days after a second weekly injection, in vivo bactericidal activity of AM toward S. aureus was diminished. This bacterial killing defect was not due to decrease phagocytosis; the in vivo binding and ingestion of bacteria were normal. The defect correlated with imparied metabolic activities associated with phagocytosis, namely a significant decrease in the reduction of nitroblue tetrazolium and the stimulation of the hexose monophosphate shunt. This may be an attractive anti-inflammatory effect in light of the destructive potential of the reactive oxygen species produced by macrophages in an arthritic circumstance.
研究表明，金会在巨噬细胞中蓄积。体外研究还表明，金对这些细胞的长期抗炎和免疫调节作用可能是其治疗类风湿性关节炎有效性的原因。然而，这些信息与体内情况的相关性在很大程度上未经检验。在本研究中，评估了硫代苹果酸金钠（AuTM）在体内给药后对大鼠肺泡巨噬细胞（AM）溶酶体酶、细菌杀伤以及与吞噬作用相关的代谢活性的影响。单次皮下注射AuTM（50mg/kg）后1天，β-葡萄糖醛酸酶、酸性磷酸酶和溶菌酶的活性受到抑制。然而，溶菌酶活性恢复正常，而β-葡萄糖醛酸酶和酸性磷酸酶的活性在随后4至12天升高。当每周给予AuTM共8周时，酸性磷酸酶和β-葡萄糖醛酸酶的活性在整个过程中均升高，而溶菌酶基本未受影响。溶酶体酶活性的增加并非由于多形核白细胞的污染。AuTm对酶活性的这些长期影响与其在体外抑制β-葡萄糖醛酸酶和酸性磷酸酶活性的作用形成显著对比。未观察到AuTM给药对调理酵母聚糖吞噬后β-葡萄糖醛酸酶释放的影响。单次注射AuTM后1天或第二次每周注射后3天，AM对金黄色葡萄球菌的体内杀菌活性降低。这种细菌杀伤缺陷并非由于吞噬作用降低；体内细菌的结合和摄取正常。该缺陷与吞噬作用相关的代谢活性受损有关，即硝基蓝四氮唑还原的显著降低和磷酸己糖旁路的刺激。鉴于巨噬细胞在关节炎情况下产生的活性氧的破坏潜力，这可能是一种有吸引力的抗炎作用。
