Anti-CD3 activation of human CD4+ T cells increases expression of the intracellular β-endorphin endopeptidase (IDE/γ-EpGE)

被引:5
作者
Sarada, B
Thiele, D
Dang, T
Lee, J
Safavia, A
Hersh, LB
Cottam, GL
机构
[1] Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA
[2] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA
[3] Univ Kentucky, Dept Biochem, Lexington, KY 40536 USA
关键词
beta-endorphin; insulin degrading enzyme (IDE); gamma-endorphin generating enzyme; hCD4C(+) T cells;
D O I
10.1016/S0165-5728(97)00268-3
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In this study, increased expression of an endopeptidase hydrolyzing beta-endorphin (beta-Ep) to gamma-endorphin (gamma-Ep, beta-Ep1-17) was observed upon immobilized anti-CD3 stimulated activation of human peripheral blood CD4(+) T cells (hCD4(+) T cells). Although freshly isolated hCD4(+) T cells are devoid of significant beta-Ep endopeptidase activity (< 0.1 nmol h(-1) 10(6) cells(-1)), activation of these cells with immobilized anti-CD3 results in a time dependent appearance of beta-Ep endopeptidase activity which reaches a maximal value of 17.4+/-0.48 nmol h(-1) 10(6) cells(-1) after 48 h of culture. Significant up-regulation of both mRNA encoding IDE/gamma-EpGE and immunoreactive protein are observed in anti-CD3 stimulated hCD4(+) T cells, indicating transcription and translation of IDE/gamma-EpGE may be elevated. No significant hydrolysis of exogenous beta-Ep is observed with intact hCD4(+) T cells whether quiescent or activated or from preparations of hCD4(+) T cell membranes. Therefore, this activity appears to be intracellular. Immunoreactive IDE/gamma-EpGE is detected inside activated hCD4(+) T cells. Analysis of metabolites generated upon hydrolysis of beta-Ep with lysed activated hCD4(+) T cell preparations identified the presence of: beta-Ep1-18, beta-Ep2-18, beta-Ep1-17, beta-Ep2-17, beta-Ep18-31, beta-Ep19-31, beta-Ep1-13, beta-Ep2-13, beta-Ep18-26, and beta-Ep20-31 as major metabolites and the majority of these are consistent with beta-Ep hydrolytic activity attributable to IDE/gamma-EpGE. (C) 1998 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:59 / 68
页数:10
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