Thrombosis in primary antiphospholipid syndrome - A pivotal role for monocyte tissue factor expression
Thrombosis in primary antiphospholipid syndrome - A pivotal role for monocyte tissue factor expression
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DOI：
10.1002/art.1780400509
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发表时间：
1997-05-01
影响因子：
--
通讯作者：
Velasco, F
中科院分区：
文献类型：
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作者：
Cuadrado, MJ;LopezPedrera, C;Velasco, F
Objective.抗磷脂综合征（APS）是一种与抗心磷脂抗体（ACL）和狼疮抗凝剂（LAC）产生相关的复发性血栓形成、妊娠丢失和血小板减少症的疾病。血栓形成的机制仍不清楚。组织因子（TF）是一种可诱导的细胞糖蛋白，是体内凝血的主要起始因子。本研究旨在探讨原发性APS患者单核细胞TF表达和促凝活性及其与血栓事件的相关性。研究了三组患者：第1组包括23名患有血栓形成的原发性APS患者，第2组包括10名没有血栓形成的原发性APS患者，第3组包括20名患有血栓形成但没有抗磷脂抗体的患者，使用20名年龄和性别匹配的健康献血者作为对照（第1组）。采用酶联免疫吸附试验（ELISA）检测抗心磷脂抗体，采用标准方法检测LAC，采用流式细胞术检测单核细胞表面TF表达。通过ELISA分析细胞裂解物中TF的量（TFAg）和可溶性TFAg血浆水平，并通过显色测定分析完整细胞和细胞裂解物上的TF相关促凝血活性（PCA-TF），采用ELISA法测定肿瘤坏死因子α（TNF α）和白细胞介素1 β（IL 1 β）的含量。与第2组（14.6+/-1.6%）、第3组（16.8+/-3.7%）和第4组（14.1+/-1.6%）相比，第1组（平均+/-SEM 50.2+/-4%阳性细胞）中TF的细胞表面表达增加。与第2组（150.8 +/-15.2）、第3组（101.4+/-14.8）和第4组（80.32+/-5.5）相比，第1组（215.8+/-11.2 pg/10（6））中的TFAg水平也升高。在第1组中，完整细胞和细胞裂解物上的PCA-TF显著增加（148.8+/-16.3单位/10（5）裂解物细胞，而第2、3和4组分别为54.5+/-11.9，38.6 +/-9.7和22.5+/-3.1），在第1组患者中，IgG型ACL阳性者TF表达程度显著增加，而IgM型ACL或LAC阳性者TF表达程度无显著增加。TNF α和IL-1 β血浆水平在任何组之间均无显著差异。这些结果表明，单核细胞TF表达直接参与原发性APS患者血栓并发症的发病机制。
Objective. The antiphospholipid syndrome (APS) is a disorder of recurrent thrombosis, pregnancy loss, and thrombocytopenia associated with the production of anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). The mechanisms of thrombus formation remain unknown. Tissue factor (TF), an inducible cell glycoprotein, is a major initiator of coagulation in vivo. The present study was therefore undertaken to investigate TF expression and procoagulant activity on monocytes from patients with primary APS and its correlation mith thrombotic events.Methods. Three groups of patients were studied: group 1 comprised 23 primary APS patients with thrombosis, group 2 consisted of 10 primary APS patients without thrombosis, and group 3 contained 20 patients with thrombosis but without antiphospholipid antibodies, Twenty age- and sex-matched healthy blood donors were used as controls (group 1). Anticardiolipin antibodies were measured by enzyme-linked immunosorbent assay (ELISA) and LAC by standard methodology, Cell surface expression of TF on monocytes was assessed by flow cytometry. The amount of TF in cell lysates (TFAg) and soluble TFAg plasma levels were analyzed by ELISA, and the TF-related procoagulant activity (PCA-TF) on intact cells and cell lysates by a chromogenic assay, Le,els of the cytokines that influence TF production, i.e., tumor necrosis factor alpha (TNF alpha) and interleukin-1 beta (IL-1 beta), were determined by ELISA.Results. Cell surface expression of TF was increased in group 1 (mean+/-SEM 50.2+/-4% positive cells) compared with group 2 (14.6+/-1.6%), group 3 (16.8+/-3.7%), and group 4 (14.1+/-1.6%). TFAg levels were also elevated in group 1 (215.8+/-11.2 pg/10(6)) compared with group 2 (150.8+/-15.2), group 3 (101.4+/-14.8), and group 4 (80.32+/-5.5). PCA-TF on intact cells and cell lysates was significantly increased in group 1 (148.8+/-16.3 units/10(5) lysate cells, compared with 54.5+/-11.9, 38.6+/-9.7, and 22.5+/-3.1 in groups 2, 3, and 4, respectively), Among group 1 patients, there was a significant increase in the degree of TF expression in those positive for IgG aCL, but not in those positive for IgM aCL or LAC. TNF alpha and IL-1 beta plasma levels did not differ significantly between any of the groups.Conclusion. These results suggest that monocyte TF expression is directly involved in the pathogenesis of thrombotic complications in patients with the primary APS.