C5a受体拮抗剂L-156,602对迟发型超敏反应的优先抑制作用。

Preferential suppression of delayed-type hypersensitivity by L-156,602, a C5a receptor antagonist.

作者信息

Tsuji R F, Uramoto M, Koshino H, Tsuji N M, Magae J, Nagai K, Yamasaki M

机构信息

Department of Agricultural Chemistry, University of Tokyo, Japan.

出版信息

Biosci Biotechnol Biochem. 1992 Oct;56(10):1686-9. doi: 10.1271/bbb.56.1686.

DOI:10.1271/bbb.56.1686

PMID:1369067

Abstract

In the course of our screening for in vivo immunomodulating substances in which sheep red blood cells (SRBC) and heat-killed Brucella abortus cells (thymus dependent and independent antigens, respectively) for antibody production assays, and trinitrobenzene sulfonic acid (TNBS) for delayed-type hypersensitivity (DTH) assay were adopted as antigens, we detected a DTH-specific suppressive activity. The producing organism was isolated from a soil sample collected in Ushiku City, Ibaraki, Japan and identified with Streptomyces sp. A1502 (FERM P-12448). The active component was identified with L-156,602, a C5a receptor antagonist. L-156,602 suppressed both TNBS-induced and TNP-SRBC-induced DTH while it enhanced antibody production against SRBC, Brucella abortus, and TNP-SRBC. L-156,602 significantly suppressed DTH induced by direct injection of type 1 helper T cells and its relevant antigen into hind-footpads, indicating that the efferent phase of DTH was affected by L-156,602. The results demonstrated that L-156,602 preferentially suppressed the DTH response.

摘要

在我们筛选体内免疫调节物质的过程中，采用绵羊红细胞（SRBC）和热灭活布鲁氏菌流产杆菌细胞（分别为胸腺依赖性和非胸腺依赖性抗原）进行抗体产生测定，采用三硝基苯磺酸（TNBS）进行迟发型超敏反应（DTH）测定作为抗原，我们检测到一种DTH特异性抑制活性。产生该活性的生物体是从日本茨城县筑波市采集的土壤样本中分离出来的，并鉴定为链霉菌属A1502（FERM P-12448）。活性成分鉴定为L-156,602，一种C5a受体拮抗剂。L-156,602抑制TNBS诱导的和TNP-SRBC诱导的DTH，同时增强针对SRBC、布鲁氏菌流产杆菌和TNP-SRBC的抗体产生。L-156,602显著抑制通过将1型辅助性T细胞及其相关抗原直接注射到后足垫诱导的DTH，表明DTH的传出阶段受到L-156,602的影响。结果表明L-156,602优先抑制DTH反应。