Pierangeli S S, Liu S W, Anderson G, Barker J H, Harris E N
Antiphospholipid Standardization Laboratory, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Circulation. 1996 Oct 1;94(7):1746-51. doi: 10.1161/01.cir.94.7.1746.
Recurrent arterial thrombosis and venous thrombosis are frequent complications of the antiphospholipid syndrome (APS). Patients produce anti-cardiolipin antibodies, but the role of these antibodies in thrombus formation is uncertain. This study used a unique CD-1 mouse model of thrombosis to determine whether anti-cardiolipin and anti-beta 2 glycoprotein 1 (beta 2 GP1) antibodies induced immunologically in these animals are thrombogenic.
The CD-1 mouse model enables measurement of the kinetics of a thrombus induced in the femoral vein of the animal. Animals are first anesthetized, then one femoral vein is exposed and subjected to a standardized, nonpenetrating "pinch" injury that induces a thrombus. The vein is trans-illuminated, and the growing thrombus is visualized on a television screen. The rate of formation and disappearance of the thrombus as well as its area can be measured by a computer attached to the television. Three groups of CD-1 mice (each group comprising seven animals) were studied. Group 1 mice were actively immunized with beta 2GP1, resulting in production of anti-beta 2GP1 and anti-cardiolipin antibodies. Group 2 mice were actively immunized with human immunoglobulin G (IgG) anti-cardiolipin antibodies and produced anti-human IgG as well as anti-cardiolipin antibodies (the latter by an idiotype-anti-idiotype reaction). These animals did not produce anti-beta 2GP1 antibodies. Group 3 mice were immunized with human serum albumin (HSA) and produced anti-HSA but not anti-cardiolipin antibodies. The kinetics of thrombus formation induced in the femoral veins of the experimental mice were compared. Results showed that the mean thrombus area as well as mean time during which thrombi persisted were significantly greater in group 1 and group 2 mice compared with group 3. There was no statistical difference between group 1 or group 2.
Demonstration of a thrombogenic effect of murine anti-cardiolipin antibodies suggests that these antibodies may be pathogenic in humans with APS.
复发性动脉血栓形成和静脉血栓形成是抗磷脂综合征（APS）常见的并发症。患者会产生抗心磷脂抗体，但这些抗体在血栓形成中的作用尚不确定。本研究使用一种独特的血栓形成CD-1小鼠模型，以确定在这些动物中免疫诱导产生的抗心磷脂抗体和抗β2糖蛋白1（β2GP1）抗体是否具有致血栓形成作用。
CD-1小鼠模型能够测量动物股静脉中诱导形成血栓的动力学过程。首先对动物进行麻醉，然后暴露一条股静脉，并对其施加标准化的非穿透性“挤压”损伤以诱导血栓形成。通过静脉透照法，在电视屏幕上观察生长中的血栓。血栓的形成和消失速率及其面积可通过连接到电视的计算机进行测量。研究了三组CD-1小鼠（每组七只动物）。第1组小鼠用β2GP1进行主动免疫，产生抗β2GP1抗体和抗心磷脂抗体。第2组小鼠用人免疫球蛋白G（IgG）抗心磷脂抗体进行主动免疫，产生抗人IgG抗体以及抗心磷脂抗体（后者通过独特型-抗独特型反应产生）。这些动物未产生抗β2GP1抗体。第3组小鼠用人血清白蛋白（HSA）进行免疫，产生抗HSA抗体但不产生抗心磷脂抗体。比较了实验小鼠股静脉中诱导血栓形成的动力学过程。结果显示，与第3组相比，第1组和第2组小鼠的平均血栓面积以及血栓持续的平均时间显著更大。第1组和第2组之间无统计学差异。
小鼠抗心磷脂抗体致血栓形成作用的证实表明，这些抗体在患有APS的人类中可能具有致病性。
