Rand J H, Wu X X, Andree H A, Lockwood C J, Guller S, Scher J, Harpel P C
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
N Engl J Med. 1997 Jul 17;337(3):154-60. doi: 10.1056/NEJM199707173370303.
The mechanisms of vascular thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome are unknown. Levels of annexin V, a phospholipid-binding protein with potent anticoagulant activity, are markedly reduced on placental villi from women with this syndrome. Hypercoagulability in such women may therefore be due to the reduction of surface-bound annexin V by antiphospholipid antibodies. To test this idea, we studied how antiphospholipid antibodies affect levels of annexin V on cultured trophoblasts and human umbilical-vein endothelial cells and how they affect the procoagulant activity of these cells.
We isolated IgG fractions from three patients with the antiphospholipid-antibody syndrome and from normal controls. These antibodies were incubated with cultured BeWo cells (a placental-trophoblast cell line), primary cultured trophoblasts, and human umbilical-vein endothelial cells. Annexin V on the cell surfaces was measured by an enzyme-linked immunosorbent assay. The coagulation times of plasma overlaid on the cells were also determined.
Trophoblasts and endothelial cells exposed to antiphospholipid-antibody IgG as compared with control IgG had reduced levels of annexin V (trophoblasts, 0.37 +/- 0.02 vs. 0.85 +/- 0.12 ng per well, P=0.02; endothelial cells, 1.6 +/- 0.04 vs. 2.1 +/- 0.05 ng per well, P=0.001). Also, trophoblasts and endothelial cells exposed to antiphospholipid-antibody IgG had faster mean (+/- SE) plasma coagulation times than cells exposed to control IgG (trophoblasts, 8.7 +/- 2.0 vs. 21.3 +/- 2.9 minutes, P=0.02; endothelial cells, 9.8 +/- 0.8 vs. 14.2 +/- 1.2 minutes, P=0.04).
Antiphospholipid antibodies reduce the levels of annexin V and accelerate the coagulation of plasma on cultured trophoblasts and endothelial cells. The reduction of annexin V levels on vascular cells may be an important mechanism of thrombosis and pregnancy loss in the antiphospholipid-antibody syndrome.
抗磷脂抗体综合征中血管血栓形成和流产的机制尚不清楚。膜联蛋白V是一种具有强大抗凝活性的磷脂结合蛋白，在患有该综合征的女性胎盘绒毛上的水平显著降低。因此，此类女性的高凝状态可能是由于抗磷脂抗体使表面结合的膜联蛋白V减少所致。为验证这一观点，我们研究了抗磷脂抗体如何影响培养的滋养层细胞和人脐静脉内皮细胞上膜联蛋白V的水平，以及它们如何影响这些细胞的促凝活性。
我们从三名抗磷脂抗体综合征患者和正常对照中分离出IgG组分。将这些抗体与培养的BeWo细胞（一种胎盘滋养层细胞系）、原代培养的滋养层细胞和人脐静脉内皮细胞一起孵育。通过酶联免疫吸附测定法测量细胞表面的膜联蛋白V。还测定了覆盖在细胞上的血浆的凝血时间。
与对照IgG相比，暴露于抗磷脂抗体IgG的滋养层细胞和内皮细胞膜联蛋白V水平降低（滋养层细胞，每孔0.37±0.02 ng对0.85±0.12 ng，P = 0.02；内皮细胞，每孔1.6±0.04 ng对2.1±0.05 ng，P = 0.001）。此外，与暴露于对照IgG的细胞相比，暴露于抗磷脂抗体IgG的滋养层细胞和内皮细胞的平均（±标准误）血浆凝血时间更快（滋养层细胞，8.7±2.0分钟对21.3±2.9分钟，P = 0.02；内皮细胞，9.8±0.8分钟对14.2±1.2分钟，P = 0.04）。
抗磷脂抗体降低培养的滋养层细胞和内皮细胞膜联蛋白V的水平，并加速血浆在这些细胞上的凝固。血管细胞膜联蛋白V水平的降低可能是抗磷脂抗体综合征中血栓形成和流产的重要机制。
