Modulation of platelet caspases and life‐span by anti‐platelet antibodies in mice

Modulation of platelet caspases and life‐span by anti‐platelet antibodies in mice
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抗血小板抗体对小鼠血小板半胱天冬酶和寿命的调节

DOI:
10.1034/j.1600-0609.2002.01444.x
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发表时间:
2002
影响因子:
3.1
通讯作者:
C. Vesin
C. Vesin
中科院分区:
医学3区
文献类型:
--
作者:
P. Piguet;C. Vesin

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摘要:抗血小板抗体与某些类型的血小板减少症有关。在这项工作中,我们研究了抗血小板抗体对血小板半胱氨酸天冬氨酸酶的激活和动力学的相反影响。用羧基荧光素标记的氟甲基酮探针(FAM-VAD-fmk)检测,兔抗血小板抗体引起严重的血小板减少,这与血浆中微粒的增加和血小板caspase的激活有关。此外,注射caspase抑制剂zVAD-fmk可防止微粒和血小板减少。相反,抗CD18mAb(M18.2)可导致血小板增多,这在野生型(+/+)小鼠中明显,但在CD18−/−或CD87−/−小鼠中则不明显,表明这两种表面分子是必需的。在注射M18.2mAb的小鼠的血小板中,caspase的激活减少,这是通过流式细胞仪检测到的VAD探针的结合减少,或者在Western blotts上看到的caspase-3原水平的增加。这些观察结果表明,首先,抗血小板抗体可以促进或抑制血小板caspase的激活,其次,caspase的激活调节血小板的寿命。
Abstract: Anti‐platelet antibodies are known to contribute to some types of thrombocytopenia. In this work we investigated anti‐platelet antibodies with opposite influence upon activation and kinetics of platelet caspases. A rabbit anti‐platelet antibody induced a profound thrombocytopenia, which was associated with an increase of microparticles in plasma and an activation of platelet caspases, as detected by the binding of a carboxyfluorescein‐labeled fluoromethyl ketone probe (FAM‐VAD‐fmk). Furthermore, microparticles and thrombocytopenia were prevented by the injection of a caspase inhibitor ZVAD‐fmk. In contrast, an anti‐CD18 mAb (M18.2) induced a thrombocytosis, due to an increased platelet life‐span and which was evident in wild‐type (+/+), but not in CD18−/− or CD87−/−, mice indicating a requirement of these two surface molecules. Activation of caspases was decreased in platelets from mice injected with the M 18.2 mAb, as evidenced by a decreased binding of the VAD probe, detected by flow cytometry, or an increase in the level of pro‐caspase‐3, seen on Western blots. These observations indicate firstly, that anti‐platelet antibodies can either promote or inhibit activation of platelet caspases, and secondly, that the activation of caspases regulates platelet life‐span.
DOI: 10.1016/s0955-0674(97)80126-3
发表时间: 1997-10-01
影响因子: 7.5
作者:
Chapman, HA
通讯作者: Chapman, HA
基因打靶产生 CD18 突变小鼠用于炎症研究。
DOI: --
发表时间: 1993
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Wilson,RW;Ballantyne,CM;Smith,CW;Montgomery,C;Bradley,A;O'Brien,WE;Beaudet,AL
通讯作者: Beaudet,AL
DOI: 10.1182/blood.v76.12.2501.2501
发表时间: 1990-12
期刊: Blood
影响因子: 20.3
作者:
Martha L. Aiken;M. Ginsberg;V. Byers-Ward;E. Plow
通讯作者: Martha L. Aiken;M. Ginsberg;V. Byers-Ward;E. Plow
DOI: 10.1073/pnas.90.18.8529
发表时间: 1993-09-15
影响因子: 11.1
作者:
SLIGH, JE;BALLANTYNE, CM;BEAUDET, AL
通讯作者: BEAUDET, AL