TRANSFORMATION OF LUPUS-INDUCING DRUGS TO CYTOTOXIC PRODUCTS BY ACTIVATED NEUTROPHILS

被引：185

作者：

JIANG, XX ^{[1
]}

KHURSIGARA, G ^{[1
]}

RUBIN, RL ^{[1
]}

机构：

[1] SCRIPPS RES INST, WM KECK AUTOIMMUNE DIS CTR, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA

来源：

SCIENCE | 1994年 / 266卷 / 5186期

关键词：

D O I：

10.1126/science.7973636

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Drug-induced lupus is a serious side effect of certain medications, but the chemical features that confer this property and the underlying pathogenesis are puzzling. Prototypes of all six therapeutic classes of lupus-inducing drugs were highly cytotoxic only in the presence of activated neutrophils. Removal of extracellular hydrogen peroxide before, but not after, exposure of the drug to activated neutrophils prevented cytotoxicity. Neutrophil-dependent cytotoxicity required the enzymatic action of myeloperoxidase, resulting in the chemical transformation of the drug to a reactive product. The capacity of drugs to serve as myeloperoxidase substrates in vitro was associated with the ability to induce lupus in vivo.

引用

页码：810 / 813

页数：4