β2-糖蛋白I和单克隆抗心磷脂抗体在流动条件下对血小板与内皮下层相互作用的影响。

Effects of beta2-glycoprotein I and monoclonal anticardiolipin antibodies in platelet interaction with subendothelium under flow conditions.

作者信息

Font Josep, Espinosa Gerard, Tàssies Dolors, Pino Marc, Khamashta Munther A, Gallart Teresa, Cervera Ricard, Escolar Ginés, Hughes Graham R V, Ingelmo Miguel, Ordinas Antoni, Reverter Joan-Carles

机构信息

Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.

出版信息

Arthritis Rheum. 2002 Dec;46(12):3283-9. doi: 10.1002/art.10634.

DOI:10.1002/art.10634

PMID:12483733

Abstract

OBJECTIVE

To evaluate whether the effect of human monoclonal anticardiolipin antibodies (aCL) on platelet interaction with the subendothelium under flow conditions is dependent on beta(2)-glycoprotein I (beta(2)GPI).

METHODS

Three monoclonal IgM aCL with anti-beta(2)GPI activity (TM1B3, GR1D5, and EY2C9) obtained from patients with antiphospholipid syndrome, a monoclonal aCL with lupus anticoagulant activity but without anti-beta(2)GPI activity (FRO) obtained from a patient with a splenic lymphoma, and a control monoclonal IgM without aCL activity were used. TM1B3, GR1D5, EY2C9, FRO, and control IgM (30 microg/ml) were added to reconstituted blood containing gel-filtered platelets (200 x 10(9)/liter), factor VIII (100 units/dl), and fibrinogen (1.5 gm/liter). Samples were perfused (wall-shear rate 800 seconds(-1)), with and without the addition of purified beta(2)GPI (20 microg/ml), through annular chambers containing collagen-rich denuded vascular segments, and the percentages of surface covered by platelets and by thrombi were evaluated.

RESULTS

No differences in the percentages of surface covered by platelets and by thrombi were observed among samples with TM1B3, GR1D5, EY2C9, FRO, and control IgM added when reconstituted blood samples without beta(2)GPI were used. However, a significant increase in the percentage of surface covered by platelets was observed in the presence of TM1B3, GR1D5, and EY2C9 but not in the presence of FRO when samples containing beta(2)GPI were used. Increased thrombi formation was induced by TM1B3 and GR1D5 but not by EY2C9 or FRO in samples with added beta(2)GPI.

CONCLUSION

Monoclonal aCL require anti-beta(2)GPI activity to promote platelet interaction with the subendothelium under flow conditions.

摘要

目的

评估人源单克隆抗心磷脂抗体（aCL）在流动条件下对血小板与内皮下层相互作用的影响是否依赖于β2-糖蛋白I（β2GPI）。

方法

使用从抗磷脂综合征患者获得的三种具有抗β2GPI活性的单克隆IgM aCL（TM1B3、GR1D5和EY2C9）、从一名脾淋巴瘤患者获得的具有狼疮抗凝活性但无抗β2GPI活性的单克隆aCL（FRO）以及一种无aCL活性的对照单克隆IgM。将TM1B3、GR1D5、EY2C9、FRO和对照IgM（30微克/毫升）添加到含有经凝胶过滤的血小板（200×10⁹/升）、因子VIII（100单位/分升）和纤维蛋白原（1.5克/升）的重组血液中。在添加和不添加纯化的β2GPI（20微克/毫升）的情况下，将样品灌注（壁面剪切速率800秒⁻¹）通过含有富含胶原蛋白的裸露血管段的环形腔室，并评估血小板和血栓覆盖的表面百分比。

结果

当使用不含β2GPI的重组血液样本时，添加TM1B3、GR1D5、EY2C9、FRO和对照IgM的样本之间，血小板和血栓覆盖的表面百分比没有差异。然而，当使用含有β2GPI的样本时，在TM1B3、GR1D5和EY2C9存在的情况下观察到血小板覆盖表面的百分比显著增加，而在FRO存在的情况下未观察到。在添加β2GPI的样本中，TM1B3和GR1D5诱导血栓形成增加，而EY2C9或FRO未诱导。