Henriksson Carola E, Hellum Marit, Landsverk Kirsti S, Klingenberg Olav, Joø Gun-Britt, Kierulf Peter
The R&D Group, Department of Clinical Chemistry, Ullevaal University Hospital, Oslo, Norway.
Thromb Haemost. 2006 Jul;96(1):29-37. doi: 10.1160/TH06-01-0052.
Monocytes/macrophages are important in disease states such as gram-negative sepsis and coronary artery disease. Following exposure to lipopolysaccharide (LPS), monocytes express tissue factor (TF), the main initiator of blood coagulation. We previously demonstrated that human monocytes treated with high concentrations of LPS, or with LPS and calcium ionophore, displayed higher TF activity than monocytes treated with only low concentrations of LPS, even though the monocytes under all conditions expressed similar amounts of cell surface TF antigen. Such restrainedTF activity is often referred to as encryption and its release as de-encryption. We also observed that the increase in TF activity, de-encryption, coincided with an increase in cell surface phosphatidylserine (PS) representing apoptosis and necrosis. In the present work, we separated LPS and LPS and calcium ionophore-treated human monocytes into two populations, one of mainly viable, PS negative cells, and one of mainly non-viable, PS positive cells, by sorting flow-cytometry. We observed that non-viable cells expressed considerably less TF antigen than viable cells. Despite this, non-viable cells were clearly more procoagulant than viable cells in two different coagulation assays. Procoagulant activity was dependent on both TF and PS. We consider the higher content of externalized PS in non-viable monocytes as the major reason for the stronger procoagulant activity of these cells. Thus, TF de-encryption appears largely to occur on PS positive, non-viable cells under these conditions. This supports the important role of PS in coagulation, and it suggests that PS expression signifying cell death, may be clinically relevant.
单核细胞/巨噬细胞在诸如革兰氏阴性败血症和冠状动脉疾病等疾病状态中起着重要作用。在接触脂多糖（LPS）后，单核细胞会表达组织因子（TF），这是血液凝固的主要启动因子。我们之前证明，用高浓度LPS或LPS与钙离子载体处理的人单核细胞，比仅用低浓度LPS处理的单核细胞表现出更高的TF活性，尽管在所有条件下单核细胞表达的细胞表面TF抗原量相似。这种受限的TF活性通常被称为加密，而其释放则称为解密。我们还观察到，TF活性的增加，即解密，与代表细胞凋亡和坏死的细胞表面磷脂酰丝氨酸（PS）的增加同时发生。在本研究中，我们通过流式细胞术分选，将用LPS以及LPS和钙离子载体处理的人单核细胞分为两个群体，一个主要是存活的、PS阴性细胞群体，另一个主要是无活力的、PS阳性细胞群体。我们观察到，无活力细胞表达的TF抗原比存活细胞少得多。尽管如此，在两种不同的凝血试验中，无活力细胞显然比存活细胞更具促凝性。促凝活性依赖于TF和PS。我们认为无活力单核细胞中外化PS含量较高是这些细胞促凝活性更强的主要原因。因此，在这些条件下，TF解密似乎主要发生在PS阳性的无活力细胞上。这支持了PS在凝血中的重要作用，并表明表明细胞死亡的PS表达可能具有临床相关性。
