Lysozyme enhances monocyte-mediated tumoricidal activity: a potential amplifying mechanism of tumor killing.
Lysozyme enhances monocyte-mediated tumoricidal activity: a potential amplifying mechanism of tumor killing.
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DOI：
10.1182/blood.v58.5.994.bloodjournal585994
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发表时间：
1981-11
期刊：
影响因子：
20.3
通讯作者：
P. Lemarbre;J. Rinehart;N. Kay;R. Vesella;H. Jacob
中科院分区：
文献类型：
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作者：
P. Lemarbre;J. Rinehart;N. Kay;R. Vesella;H. Jacob
单核巨噬细胞已被公认为某些人类肿瘤的体外细胞毒性效应细胞。这种作用的机制尚不清楚。溶菌酶（一种由单核吞噬细胞大量合成的阳离子酶）水平的增加与对可移植动物肿瘤的抗性增加有关。在这项研究中，我们提供的证据表明，从白血病患者的尿液中分离的人溶菌酶，对人单核细胞肿瘤细胞的杀细胞活性有显着的增强作用。此外，溶菌酶暴露的单核细胞纳入亮氨酸的量增加，这表明单核细胞能够通过分泌内源性成分来放大其自身的代谢活化。三-N-乙酰-葡糖胺是溶菌酶活性位点的竞争性抑制剂，可抑制其杀细胞活性。相反，鱼精蛋白，一个外来的，但同样带正电荷的分子，增加单核细胞介导的肿瘤细胞毒性;这种鱼精蛋白的作用是否定的肝素。我们的结论是，溶菌酶，至少部分地通过其正电荷，是能够增强体外单核细胞肿瘤细胞的细胞毒性，其在体内分泌可能会增强单核细胞-肿瘤细胞相互作用。
The mononuclear phagocyte is well established as an in vitro cytotoxic effector cell for certain human tumors. The mechanism(s) for this action remains unclear. Increased levels of lysozyme, a cationic enzyme synthesized in large amounts by mononuclear phagocytes, are associated with increased resistance to transplantable animal tumors. In this study, we provide evidence that human lysozyme, isolated from the urine of leukemic patients, has marked potentiating effects on human monocyte-tumor-cell cytocidal activity. In addition, lysozyme-exposed monocytes incorporate increased quantities of leucine, suggesting that monocytes are capable of amplifying their own metabolic activation by secreting an endogenous constituent. Tri-N-acetyl-glucosamine, a competitive inhibitor for the active site of lysozyme, inhibits cytocidal activity. Conversely, protamine, an extraneous albeit similarly positively charged molecule, increases monocyte-mediated tumor cytotoxicity; this protamine effect is negated by heparin. We conclude that lysozyme, at least partially by its positive charge, is capable of enhancing in vitro monocyte tumor cell cytotoxicity; its in vivo secretion may potentiate monocyte-tumor-cell interaction.