MECHANISMS OF DRUG ALLERGY

药物过敏的机制

• 批准号: 3281580
• 负责人: KENNETH P. MATHEWS
• 金额: $ 7.53万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-03-01 至 1986-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281580
• 关键词: autoantibody; covalent bond; drug hypersensitivity; drug metabolism; enzyme complex; enzyme linked immunosorbent assay; erythrocytes; esterase; human subject; immunization; immunopharmacology; protein glutamine gamma glutamyltransferase

It has been thought that there must be covalent binding of low molecular weight drugs, or their metabolites, to larger carrier molecules in order for such drugs and other haptens to stimulate an immune or allergic response. However, since delineation of this mechanism for penicillin allergy was reported over 20 years ago, little progress has been made in identifying reactive metabolites which could initiate allergic responses to other drugs. This project aims to explore the following alternatives: (1) enzyme-inhibitor drugs may stimulate immune responses to drugs when they are firmly bound to their enzymes; (2) host enzymes may covalently link stable drugs with protein carriers, thereby conferring antigenicity; (3) some aspects of drug allergy may be due to drug-induced autoimmune responses, and (4) in vitro binding of drugs or their metabolites to erthrocyte stroma may provide a basis for urgently needed diagnostic tests for drug allergy.

人们一直认为，低分子的结合必须是共价结合， 将药物或其代谢物按顺序重放到较大的载体分子上， 对于此类药物和其他半抗原刺激免疫或过敏 反应 然而，由于青霉素的这种机制的描述， 过敏症是20多年前报道的，在这方面几乎没有进展。 鉴定可能引发过敏反应的反应性代谢物， 其他药物。 本项目旨在探索以下替代方案：（1） 酶抑制剂药物可能会刺激免疫反应的药物时， 与其酶牢固结合;（2）宿主酶可以共价连接 具有蛋白质载体的稳定药物，从而赋予抗原性;（3） 药物过敏的某些方面可能是由于药物诱导的自身免疫性 反应，以及（4）药物或其代谢物与 红细胞间质可能为急需的诊断试验提供基础 因为药物过敏

项目成果

Generation of drug metabolite antigenicity in the intestinal mucosa.

在肠粘膜中产生药物代谢物抗原性。

• DOI: 10.1016/0162-3109(86)90051-2
• 发表时间: 1986
• 期刊: Immunopharmacology
• 作者: Wu,C;Mathews,KP
• 通讯作者: Mathews,KP

Conversion of leukotrienes A4 to C4 in cell-free systems.

在无细胞系统中白三烯 A4 转化为 C4。

• DOI: 10.1016/0006-291x(86)90530-9
• 发表时间: 1986
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Wu,C