ARGININE-DEPENDENT GENERATION OF REACTIVE NITROGEN INTERMEDIATES IS INSTRUMENTAL IN THE IN-VITRO KILLING OF PROTOSCOLECES OF ECHINOCOCCUS-MULTILOCULARIS BY ACTIVATED MACROPHAGES
ARGININE-DEPENDENT GENERATION OF REACTIVE NITROGEN INTERMEDIATES IS INSTRUMENTAL IN THE IN-VITRO KILLING OF PROTOSCOLECES OF ECHINOCOCCUS-MULTILOCULARIS BY ACTIVATED MACROPHAGES
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DOI：
10.1111/j.1365-3024.1993.tb00575.x
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发表时间：
1993-11-01
影响因子：
2.2
通讯作者：
STADECKER, MJ
中科院分区：
文献类型：
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作者：
KANAZAWA, T;ASAHI, H;STADECKER, MJ
本研究检测了多房棘球绦虫原头蚴与活化的小鼠巨噬细胞之间的相互作用。经干扰素 -γ（IFN -γ）或IFN -γ加脂多糖活化的腹腔巨噬细胞（PM）显示出显著的原头蚴杀伤活性。用热灭活的特异性小鼠感染血清而非正常血清预处理寄生虫，会使其更易被PM杀伤。N(G)-单甲基 -L -精氨酸（一种L -精氨酸的竞争性抑制剂）完全抑制了活化PM的杀伤活性，而在无精氨酸培养基中补充L -精氨酸则恢复了活化PM的杀伤特性。结果表明，活化的PM在体外具有杀伤多房棘球绦虫原头蚴的能力，并提示活性氮中间体（RNI）在该机制中起重要作用。一种氧介导的机制似乎未起作用，因为活性氧清除剂未降低杀伤活性。超氧化物歧化酶（SOD）增强了精氨酸依赖的杀伤机制，可能是因为SOD可延长一氧化氮的作用。活化巨噬细胞分泌的RNI可能在体内预防多房棘球绦虫感染的传播中起重要作用。
The interaction between protoscoleces of Echinococcus multilocularis and activated murine macrophages was examined in this study. Marked protoscolicidal activity was displayed by peritoneal macrophages (PM) activated with interferon-gamma (IFN-gamma), or IFN-gamma plus lipopolysaccharide. Pretreatment of the parasites with heat-inactivated specific murine infection serum, but not with normal serum rendered them more susceptible to PM killing. N(G)-monomethyl-L-arginine, a competitive inhibitor of L-arginine completely inhibited the killing activity of actitvated PM, while reconstitution of arginine-free medium with L-arginine restored the killing properties of the activated PM. The results show that activated PM have the ability to kill E. multilocularis protoscoleces in vitro and suggest that reactive nitrogen intermediates (RNI) play an important role in the mechanism. An oxygen-mediated mechanism didnot appear to play a role because scavengers of reactive oxygen species did not reduce the killing activity. The arginine-dependent killing mechanism was enhanced by superoxide dismutase (SOD), probably because SOD might prolong the effect of nitric oxide. Secretion of RNI by activated macrophages may be capable of a significant role in preventing of the dissemination of E. multilocularis infection in vivo.