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首页> 外文期刊>World Journal of Gastroenterology >Activation of human colon mast cells through proteinase activated receptor-2
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Activation of human colon mast cells through proteinase activated receptor-2

机译：通过蛋白酶激活受体2激活人结肠肥大细胞

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摘要

AIM: To investigate the ability of agonists of PAR-2 to stimulate release of tryptase and histamine from human colon mast cells and the potential mechanisms. METHODS: Enzymatically dispersed cells from human colons were challenged with tc-LIGRLO, tc-OLRGIL, SLIGKV, VKGILS, trypsin, anti-IgE or calcium ionophore A23187, and the cell supernatants after challenge were collected. Tryptase release was determined with a sandwich ELISA procedure and histamine release was measured using a glass fibre-based fluorometric assay. RESULTS: Both PAR-2 agonists tc-LIGRLO-NH_2 and SLIGKV-NH_2 were able to induce dose dependent release of tryptase and histamine from colon mast cells. More than 2.5 fold increase in both tryptase and histamine release was provoked by 100μmol/mL tc-LIGRLO-NH_2, in comparison with only 2.0 fold increase being stimulated by SLIGKV-NH_2. The reverse peptides tc-OLRGIL-NH_2 and VKGILS -NH_2 at the concentrations tested had no effect on the release of these two mediators. The maximum tryptase release elicited by tc-LIGRLO-NH_2 was similar to that induced by anti-IgE (10μg/mL) or calcium ionophore (1μg/mL), though the latter was a more potent stimulus for histamine release. Both histamine and tryptase release in response to tc-LIGRLO-NH_2 were completed within 3 min. Trypsin at concentrations from 1.0 to 100μg/mL was capable of provoking a dose dependent release of tryptase as well as histamine with a maximum of 16 ng/mL tryptase and 14 ng/mL histamine release being achieved. An approximately 80% and 70% inhibition of trypsin induced release of tryptase and histamine were observed with SBTI, respectively. Pretreatment of cells with metabolic inhibitors or pertussis toxin abolished the actions of tc-LIGRLO-NH_2, SLIGKV-NH_2 and trypsin. CONCLUSION: The agonists of PAR-2 and trypsin are potent secretagogues of human colon mast cells, which are likely to contribute to the development of inflammatory disorders in human gut.
机译：目的：研究PAR-2激动剂刺激人结肠肥大细胞释放类胰蛋白酶和组胺的能力及其潜在机制。方法：用tc-LIGRLO，tc-OLRGIL，SLIGKV，VKGILS，胰蛋白酶，抗IgE或钙离子载体A23187攻击人结肠中酶分散的细胞，并收集攻击后的细胞上清液。用三明治ELISA程序确定类胰蛋白酶的释放，并使用基于玻璃纤维的荧光测定法测量组胺的释放。结果：PAR-2激动剂tc-LIGRLO-NH_2和SLIGKV-NH_2均能诱导结肠肥大细胞中类胰蛋白酶和组胺的剂量依赖性释放。 100μmol/ mL tc-LIGRLO-NH_2引起的类胰蛋白酶和组胺释放增加了2.5倍以上，而SLIGKV-NH_2刺激仅增加了2.0倍。所测试浓度的反向肽tc-OLRGIL-NH_2和VKGILS-NH_2对这两种介质的释放没有影响。 tc-LIGRLO-NH_2诱导的最大类胰蛋白酶释放与抗IgE（10μg/ mL）或钙离子载体（1μg/ mL）诱导的最大相似，尽管后者是更有效的组胺释放刺激。响应tc-LIGRLO-NH_2的组胺和类胰蛋白酶释放均在3分钟内完成。浓度为1.0至100μg/ mL的胰蛋白酶能够引起剂量依赖性的类胰蛋白酶和组胺的释放，最大量为16 ng / mL的类胰蛋白酶和14 ng / mL的组胺释放。用SBTI分别观察到约80％和70％的胰蛋白酶抑制诱导了胰蛋白酶和组胺的释放。用代谢抑制剂或百日咳毒素预处理细胞可以消除tc-LIGRLO-NH_2，SLIGKV-NH_2和胰蛋白酶的作用。结论：PAR-2和胰蛋白酶的激动剂是人结肠肥大细胞的强促分泌剂，可能促进人肠炎性疾病的发展。

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  • 来源
    《World Journal of Gastroenterology》 |2004年第3期|p.327-331|共5页
  • 作者

    Shao-Heng He; Yong-Song He; Hua Xie;

  • 作者单位

    Allergy and Inflammation Research Institute, Shantou University Medical College, 22 Xin-Ling Road, Shantou 515031, Guangdong Province, China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 消化系及腹部疾病;
  • 关键词

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