Pharmacological analysis for mechanisms of GPI‐80 release from tumour necrosis factor‐α‐stimulated human neutrophils
Pharmacological analysis for mechanisms of GPI‐80 release from tumour necrosis factor‐α‐stimulated human neutrophils
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肿瘤坏死因子-α刺激的人中性粒细胞释放 GPI-80 机制的药理学分析
DOI：
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发表时间：
2002
影响因子：
7.3
通讯作者：
F. Sendo
中科院分区：
文献类型：
--
作者：
T. Nitto;Y. Araki;Y. Takeda;F. Sendo
GPI‐80是一种糖基磷脂酰肌醇（GPI）锚定蛋白，最初在人中性粒细胞上发现，在调节β2整合素功能中起作用。先前的研究表明GPI‐80位于分泌囊泡中。它也以可溶性形式存在于类风湿性关节炎患者的滑液中，以及甲酰基-甲硫基-亮基-苯丙氨酸-刺激中性粒细胞的培养上清中。为了了解GPI‐80在刺激条件下的行为，我们研究了肿瘤坏死因子（TNF）‐α对其表达和释放的影响。并利用多种药理工具探讨了其释放机制。TNF‐α诱导人中性粒细胞以浓度和时间依赖性的方式释放GPI‐80（分别在1 - 100 μ ml−1和30-120 min范围内），但不影响表面GPI‐80水平。在相同浓度下，细胞松弛素B、染料木素和SB203580抑制TNF - α刺激的GPI - 80释放和中性粒细胞粘附，而PD98059没有。此外，阻断Mac - 1组分特异性单克隆抗体（CD11b和CD18）可抑制TNF - α诱导的GPI - 80释放。抗氧化剂（吡咯烷二硫代氨基甲酸酯和N -乙酰- L -半胱氨酸）抑制TNF - α刺激下GPI - 80的释放，但超氧化物歧化酶没有。抗氧化剂而非超氧化物歧化酶降低细胞内氧化状态。这些发现表明TNF - α刺激的GPI - 80从人中性粒细胞释放依赖于通过β2整合素的粘附。他们还表明，细胞松弛素B、染料木素和SB203580通过抑制细胞粘附信号来抑制GPI - 80的释放，而不是直接影响其分泌。最后，我们认为GPI - 80的释放涉及氧化还原状态下的细胞内变化。
GPI‐80, a glycosylphosphatidylinositol (GPI)‐anchored protein initially identified on human neutrophils, plays a role(s) in the regulation of β2 integrin function. Previous studies have shown that GPI‐80 is sublocated in secretory vesicles. It is also found in soluble form in the synovial fluid of rheumatoid arthritis patients, and in the culture supernatant of formyl‐methionyl‐leucyl‐phenylalanine‐stimulated neutrophils. To understand the behaviour of GPI‐80 under conditions of stimulation, we investigated the effects of tumour necrosis factor (TNF)‐α on its expression and release. We also probed the mechanism of its release with various pharmacologic tools. TNF‐α induced the release of GPI‐80 from human neutrophils in a concentration‐ and time‐dependent manner (in the range of 1–100 u ml−1 and 30–120 min, respectively), but did not affect surface GPI‐80 levels. Cytochalasin B, genistein, and SB203580 but not PD98059 inhibited TNF‐α‐stimulated GPI‐80 release and neutrophil adherence at the same concentration. In addition, TNF‐α‐induced GPI‐80 release was inhibited by blocking monoclonal antibodies specific to components of Mac‐1 (CD11b and CD18). Antioxidants (pyrrolidine dithiocarbamate and N‐acetyl‐L‐cysteine) inhibited GPI‐80 release by TNF‐α stimulation, but superoxide dismutase did not. Antioxidants but not superoxide dismutase reduced an intracellular oxidation state. These findings indicate that TNF‐α‐stimulated GPI‐80 release from human neutrophils depends upon adherence via β2 integrins. They also suggest that cytochalasin B, genistein, and SB203580 inhibit GPI‐80 release by suppressing signals for cell adherence, rather than by a direct effect on its secretion. Finally, we suggest that GPI‐80 release involves an intracellular change in a redox state.
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影响因子：
4.4
作者：
J. Allport;H. Ding;A. Ager;D. Steeber;T. Tedder;F. Luscinskas
通讯作者：
J. Allport;H. Ding;A. Ager;D. Steeber;T. Tedder;F. Luscinskas
影响因子：
4.4
作者：
D. Bass;J. W. Parce;L. Dechatelet;P. Szejda;M. Seeds;M. Thomas
通讯作者：
D. Bass;J. W. Parce;L. Dechatelet;P. Szejda;M. Seeds;M. Thomas
影响因子：
4.4
作者：
James D. Griffin;O. Spertini;T. Ernst;M. Belvin;H. Levine;Y. Kanakura;T. Tedder
通讯作者：
James D. Griffin;O. Spertini;T. Ernst;M. Belvin;H. Levine;Y. Kanakura;T. Tedder
DOI：
10.1172/jci113928
发表时间：
1989-02
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
G. Tonnesen;Donald C. Anderson;T. A. Springer;A. Knedler;N. Avdi;Peter M. Henson
通讯作者：
G. Tonnesen;Donald C. Anderson;T. A. Springer;A. Knedler;N. Avdi;Peter M. Henson
影响因子：
15.9
作者：
NATHAN, CF
通讯作者：
NATHAN, CF