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【Blood】中性粒细胞来源的微粒上整合素Mβ2 (Ma
Elzbieta Pluskota1, Neil M. Woody1, Dorota Szpak1, Christie M. Ballantyne2, Dmitry A. Soloviev1, Daniel I. Simon3, and Edward F. Plow1
1 Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic, OH; 2 Baylor College of Medicine and Methodist DeBakey Heart Center, Houston, TX; and 3 University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH
Leukocyte-derived microparticles (MPs) are markers of cardiovascular diseases and contribute to pathogenesis by their interaction with various cell types. The presence and activation state of a multifunctional leukocyte receptor, integrin Mβ2 (CD11b/18), on MPs derived from human neutrophils (PMNs) were examined. Mβ2 expression was significantly enhanced on MPs derived from stimulated compared with resting PMNs. Furthermore, Mβ2 on MPs from stimulated but not resting PMNs was in an activated conformation because it was capable of binding activation-specific monoclonal antibodies (CBRM1/5 and mAb24) and soluble fibrinogen. MPs expressing active Mβ2 interacted with and were potent activators of resting platelets as assessed by induction of P-selectin expression and activation of IIbβ3. With the use of function-blocking antibodies and MPs obtained from –/–-deficient mice, we found that engagement of GPIb on platelets by Mβ2 on MPs plays a pivotal role in MP binding. Platelet activation by MPs occurs by a pathway dependent on Akt phosphorylation. PSGL-1/P-selectin interaction also is involved in the conjugation of MPs to platelets, and the combination of blocking reagents to both Mβ2/GPIb and to PSGL-1/P-selectin completely abrogates MP-induced platelet activation. Thus, cooperation of these 2 receptor/counterreceptor systems regulates the prothrombotic properties of PMN-derived MPs. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Expression, activation, and function of integrin Mβ2 (Mac-1) on neutrophil-derived microparticles
整合素Mβ2 (Mac-1)在嗜中性粒细胞来源的微粒中的表达活化和功能
Leukocyte-derived microparticles (MPs) are markers of cardiovascular diseases and contribute to pathogenesis by their interaction with various cell types. The presence and activation state of a multifunctional leukocyte receptor, integrin Mβ2 (CD11b/18), on MPs derived from human neutrophils (PMNs) were examined. Mβ2 expression was significantly enhanced on MPs derived from stimulated compared with resting PMNs. Furthermore, Mβ2 on MPs from stimulated but not resting PMNs was in an activated conformation because it was capable of binding activation-specific monoclonal antibodies (CBRM1/5 and mAb24) and soluble fibrinogen. MPs expressing active Mβ2 interacted with and were potent activators of resting platelets as assessed by induction of P-selectin expression and activation of IIbβ3. With the use of function-blocking antibodies and MPs obtained from –/–-deficient mice, we found that engagement of GPIb on platelets by Mβ2 on MPs plays a pivotal role in MP binding. Platelet activation by MPs occurs by a pathway dependent on Akt phosphorylation. PSGL-1/P-selectin interaction also is involved in the conjugation of MPs to platelets, and the combination of blocking reagents to both Mβ2/GPIb and to PSGL-1/P-selectin completely abrogates MP-induced platelet activation. Thus, cooperation of these 2 receptor/counterreceptor systems regulates the prothrombotic properties of PMN-derived MPs.
白细胞来源的微粒(MPs)是心血管疾病的标志，通过与不同类型的细胞相互作用促进发病。在人类中性白细胞（PMNs）来源的微粒中检测到多功能白细胞受体整合素Mβ2 (CD11b/18)的存在和活化状态。与休眠的中性粒细胞（PMNs）相比，受刺激的中性粒细胞的微粒中Mβ2的表达显著增强。此外，受激的中性粒细胞的微粒是处于活化构象，因为它能够结合活化的特异性单克隆抗体(CBRM1/5 and mAb24)和可溶性纤维蛋白原，而休眠的中性粒细胞没有活化。表达Mβ2的微粒与休眠的血小板相互作用，通过评估它对血小板P-选择素的诱导和对IIbβ3的活化，认为它是休眠血小板有效的活化物。利用功能阻断抗体和Mβ2缺失小鼠的微粒，发现血小板上的GPIb与微粒上的Mβ2相互作用在微粒结合中发挥轴心作用。血小板通过微粒的活化依赖Akt的磷酸化。PSGL-1/P-selectin相互作用也参与微粒对血小板的结合，Mβ2/GPIb和PSGL-1/P-selectin的阻断剂结合使用会完全消除微粒诱导的血小板活化。因此，这两个受体/反受体系统的相互作用调节中性粒细胞来源的微粒的趋血栓阻塞性。
编译
整合素Mβ2 (Mac-1)在嗜中性粒细胞来源的微粒中的表达活化和功能
白细胞来源的微粒(MPs)是心血管疾病的标志，通过与不同类型的细胞相互作用促进发病。在人类中性白细胞（PMNs）来源的微粒中检测到多功能白细胞受体整合素Mβ2 (CD11b/18)的存在和活化状态。与休眠的中性粒细胞（PMNs）相比，受刺激的中性粒细胞的微粒中Mβ2的表达显著增强。此外，受激的中性粒细胞的微粒是处于活化构象，因为它能够结合活化的特异性单克隆抗体(CBRM1/5 and mAb24)和可溶性纤维蛋白原，而休眠的中性粒细胞没有活化。表达Mβ2的微粒与休眠的血小板相互作用，通过评估它对血小板P-选择素的诱导和对IIbβ3的活化，认为它是休眠血小板有效的活化物。利用功能阻断抗体和Mβ2缺失小鼠的微粒，发现血小板上的GPIb与微粒上的Mβ2相互作用在微粒结合中发挥轴心作用。血小板通过微粒的活化依赖Akt的磷酸化。PSGL-1/P-selectin相互作用也参与微粒对血小板的结合，Mβ2/GPIb和PSGL-1/P-selectin的阻断剂结合使用会完全消除微粒诱导的血小板活化。因此，这两个受体/反受体系统的相互作用调节中性粒细胞来源的微粒的趋血栓阻塞性。（丁香） [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-05-23 17:11
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