Polymorphism in the tissue factor region is associated with basal but not endotoxin-induced tissue factor-mRNA levels in leukocytes

OBJECTIVE: Tissue factor (TF) plays a central role during disseminated intravascular coagulation (DIC) in sepsis. We hypothesized that a frequent D/I polymorphism, at nucleotide position -1208 in the promoter region, could influence TF-mRNA and downstream coagulation. METHODS: Basal- and lipopolysaccharide (LPS)-induced TF-mRNA expression, microparticle-associated TF-procoagulant activity and coagulation were determined in healthy men (n = 74) before and after endotoxin (LPS) infusion (2 ng kg(-1)). Basal values of TF-mRNA ranged between 34 and > 37.5 cycles. RESULTS: Baseline TF-mRNA levels significantly differed between genotypes: I/I carriers had almost 2-fold higher TF-mRNA levels compared to D/D carriers at baseline (P < 0.01). In accordance, higher levels of microparticle-associated TF-procoagulant activity could be seen in I/I carriers. However, the genotype did not affect basal or LPS-induced levels of prothrombin fragment F1+2, D-dimer or cytokines including tumor necrosis factor and interleukin-6. CONCLUSION: The TF-1208 polymorphism is functional in that it regulates basal TF-mRNA in circulating monocytes and circulating microparticle-associated TF-procoagulant activity in vivo, but does not influence the relative increase in TF-mRNA or coagulation activation during low-grade endotoxemia.     

Effect of Nitric Oxide on the Oxygen Metabolism and Growth of E. faecalis

Gastro-intestinal mucosal cells have a potent mechanism to eliminate a variety of pathogens using enzymes that generate reactive oxygen species and/or nitric oxide (NO). However, a large number of bacteria survive in the intestine of human subjects. Enterococcus faecalis (E. faecalis) is a Gram-positive bacterium that survives not only in the intestinal lumen but also within macrophages generating NO. It has been reported that E. faecalis generated the superoxide radical (O₂⁻). To elucidate the role of O₂⁻ and NO in the mechanism for the pathogen surviving in the intestine and macrophages, we studied the role and metabolism of O₂⁻ and NO in and around E. faecalis. Kinetic analysis revealed that E. faecalis generated 0.5 µmol O₂⁻/min/10⁸ cells in a glucose-dependent manner as determined using the cytochrome c reduction method. The presence of NOC12, an NO donor, strongly inhibited the growth of E. faecalis without affecting in the oxygen consumption. However, the growth rate of NOC12-pretreated E. faecalis in NO-free medium was similar to that of untreated cells. Western blotting analysis revealed that the NOC12-treated E. faecalis revealed a large amount of nitrotyrosine-posititive proteins; the amounts of the modified proteins were higher in cytosol than in membranes. These observations suggested that O₂⁻ generated by E. faecalis reacted with NO to form peroxinitrite (ONOO⁻) that preferentially nitrated tyrosyl residues in cytosolic proteins, thereby reversibly inhibited cellular growth. Since E. faecalis survives even within macrophages expressing NO synthase, similar metabolism of O₂⁻ and NO may occur in and around phagocytized macrophages.     

Thrombomodulin phenotype of a distinct monocyte subtype is an independent prognostic marker for disseminated intravascular coagulation

Introduction

Thrombomodulin, which is expressed solely on monocytes, along with tissue factor (TF), takes part in coagulation and inflammation. Circulating blood monocytes can be divided into 3 major subtypes on the basis of their receptor phenotype: classical (CD14^brightCD16^negative, CMs), inflammatory (CD14^brightCD16^positive; IMs), and dendritic cell-like (CD14^dimCD16^positive DMs). Monocyte subtype is strongly regulated, and the balance may influence the clinical outcomes of disseminated intravascular coagulation (DIC). Therefore, we investigated the phenotypic difference in thrombomodulin and TF expression between different monocyte subtypes in coagulopathy severity and prognosis in patients suspected of having DIC.

Methods

In total, 98 patients suspected of having DIC were enrolled. The subtypes of circulating monocytes were identified using CD14 and CD16 and the thrombomodulin and TF expression in each subtype, expressed as mean fluorescence intensity, was measured by flow cytometry. Plasma level of tissue factor was measured by ELISA. In cultures of microbead-selected, CD14-positive peripheral monocytes, lipopolysaccharide (LPS)- or interleukin-10-induced expression profiles were analyzed, using flow cytometry.

Results

The proportion of monocyte subtypes did not significantly differ between the overt and non-overt DIC groups. The IM thrombomodulin expression level was prominent in the overt DIC group and was well correlated with other coagulation markers. Of note, IM thrombomodulin expression was found to be an independent prognostic marker in multivariate Cox regression analysis. In addition, in vitro culture of peripheral monocytes showed that LPS stimulation upregulated thrombomodulin expression and TF expression in distinct populations of monocytes.

Conclusions

These findings suggest that the IM thrombomodulin phenotype is a potential independent prognostic marker for DIC, and that thrombomodulin-induced upregulation of monocytes is a vestige of the physiological defense mechanism against hypercoagulopathy.     

Tissue factor and IL8 production by P-selectin-dependent platelet–monocyte aggregates in whole blood involves phosphorylation of Lyn and is inhibited by IL10

Summary. Background: P‐selectin and CD40L expressed by activated platelets induce tissue factor (TF) and inflammatory cytokines in monocytes, but little is known of the cellular signaling pathways involved. The anti‐inflammatory cytokine IL10 reduces atherosclerotic plaque formation. Objectives: To evaluate the importance of P‐selectin upon platelet–monocyte aggregate (PMA) formation in thrombin receptor activator peptide (TRAP) stimulated whole blood, the P‐selectin–P‐selectin glycoprotein ligand (PSGL)‐1‐induced cellular signaling pathway, and the effects of IL10 on these functions. Methods: TF, IL8, and monocyte chemotactic protein‐1 (MCP‐1) production, PMAs and phosphorylation of Lyn were analyzed in whole blood, purified monocytes, and vitamin D₃‐differentiated U‐937 cells stimulated with TRAP or P‐selectin with or without IL10. Anti‐P‐selectin or anti‐CD40L antibodies (Abs), Src‐kinases inhibitors, SU6656 or PP2, were added in some experiments. Results: TRAP and P‐selectin increased TF, IL8, and MCP‐1 mRNA in whole blood and purified monocytes. Anti‐P‐selectin Ab reduced TRAP‐induced PMA formation by 80 ± 2% (P = 0.001) and production of TF (P = 0.04) and IL8 (P = 0.01). IL10 and SU6656 had no effect on PMA formation, although both significantly reduced TF (P = 0.002 and P = 0.02) and IL8 (P = 0.009 and P = 0.001) mRNA upon TRAP and P‐selectin stimulation. Induced Lyn phosphorylation in monocytes was diminished by SU6656 (P = 0.02), anti‐P‐selectin Ab (P = 0.02), and IL10 (P = 0.03) upon TRAP or P‐selectin stimulation. These results were confirmed in the vitamin D₃‐differentiated U‐937 cells. Conclusions: The formation of PMAs in whole blood was P‐selectin‐dependent in the long term. P‐selectin–PSGL‐1‐induced TF and IL8 expression through Lyn phosphorylation, and part of the inhibitory effect of IL10 depends on reduced phosphorylation.     

Coagulation intravasculaire disséminée en réanimation : utilisation des inhibiteurs de la voie du facteur tissulaire

In most disseminated intravascular coagulation (DIC) syndromes, the culprit is an inappropriate exposition of tissue factor (TF) to the circulation. This contact results from major tissue lesions, abnormal TF expression by circulating cells (monocytes) in Gram⁺ or Gram^– sepsis, or TF expression by malignant cells. TF exposition to plasma leads to the activation of the coagulation cascade, and to a subsequent thrombin generation. Moreover, the binding of TF to its natural ligand, factor VII, leads to intracellular signalisation which induces the synthesis of proinflamatory cytokines, with subsequent leukocyte activation and majoration of the pathophysiological process. The TF pathway can be specifically inhibited by two means: 1. Infusion of recombinant TFPI, which is the natural inhibitor of the TF-factor VIIa complex, or 2. Infusion of an inactive recombinant substitute for FVIIa, FFR-VIIa. These two molecules are currently tested in humans, the first one in sepsis-related DIC, and the second one in acute respiratory distress syndrome, another condition associated with TF pathway activation.     

No evidence for the presence of tissue factor in high‐purity preparations of immunologically isolated eosinophils

Summary. Background: To date, there is no unequivocal opinion on whether human eosinophils express tissue factor (TF). Therefore, we studied the expression of TF protein and activity in resting or stimulated immunologically purified human eosinophils. Methods and results: By use of immunologic isolation, we achieved over 96% purity of eosinophil preparations, and contamination by CD14‐positive cells was below 0.3%. Flow cytometric [fluorescence‐activated cell sorting (FACS)] analysis of eosinophils revealed no surface expression of TF antigen in resting or stimulated eosinophils. Immunoblotting of eosinophil lysates did not show any TF protein under resting or stimulated conditions. The lysates of resting or stimulated eosinophils contained no detectable levels of TF procoagulant activity. In contrast, monocytes, stimulated in plasma or medium, possessed readily detectable TF levels on the cell surface and in cell lysates as detected by FACS and immunoblotting. This was active TF antigen, as confirmed by TF activity assay (19.2 ± 4.2 and 28.6 ± 3.1 mU per 10⁶ cells, stimulated in medium or plasma, respectively). We found no detectable TF mRNA levels in resting or stimulated eosinophils by real‐time polymerase chain reaction (PCR), whereas in monocytes TF mRNA levels were significantly increased after stimulation. Conclusions: Our data indicate that there is no evidence for TF expression in high‐purity preparations of immunologically isolated eosinophils.     

Deficiency of Lung Antioxidants in Idiopathic Pulmonary Arterial Hypertension

Idiopathic pulmonary arterial hypertension (IPAH) is associated with lower levels of the pulmonary vasodilator nitric oxide (NO) and its biochemical reaction products (nitrite [NO₂ ⁻], nitrate [NO₃ ⁻]), in part, due to the reduction in pulmonary endothelial NO synthesis. However, NO levels are also determined by consumptive reactions, such as with superoxide to form peroxynitrite, which subsequently may generate stable products of nitrotyrosine (Tyr‐NO₂) and/or NO₃ ⁻. In this context, superoxide dismutase (SOD) preserves NO in vivo by scavenging superoxide and preventing the consumptive reactions. Here, we hypothesized that reactive oxygen species (ROS) consumption of NO may contribute to the low NO level and development of pulmonary hypertension. To test this, nitrotyrosine and antioxidants glutathione (GSH), glutathione peroxidase (GPx), catalase, and SOD were evaluated in IPAH patients and healthy controls. SOD and GPx activities were decreased in IPAH lungs (all p < 0.05), while catalase and GSH activities were similar among the groups (all p > 0.2). SOD activity was directly related to exhaled NO (eNO) (R ²= 0.72, p= 0.002), and inversely related to bronchoalveolar lavage (BAL) NO₃ ⁻ (R ²=–0.73, p= 0.04). Pulmonary artery pressure (PAP) could be predicted by a regression model incorporating SOD, GPx, and NO₃ values (R ²= 0.96, p= 0.01). These findings suggest that SOD and GPx are associated with alterations in NO and PAP in IPAH.     

Interactions between pH,reactive species,and cells in plasma-activated water can remove algae

Lightning strikes cause nitrogen to dissolve in water and form reactive nitrogen and oxygen species, which form natural fertilizers that can be absorbed through plant roots. Such processes during rainstorm events can be simulated by applying plasma to a solution. Plasma-activated water (PAW) has great potential as a source of various dissolved reactive chemical species. Different mixtures of species are produced using different solution compositions. Here, basil seeds were grown in PAW to prevent blooms of Chlorella vulgaris and ion chromatography and UV-vis spectroscopy were used to quantify reactive ions. NO₂⁻, NO₃⁻, and H₂O₂ were found to be key to the antialgal effect. Secondary reactive ions such as peroxynitrite (ONOO⁻, ONOOH) were also involved. The antialgal effect was strongly related to the pH around the algal cells. Acidification was predominantly caused by the generation of NO₂⁻ and H₂O₂. After two weeks monitoring basil growth, the antifungal properties were preserved, few reactive oxygen species formed in the plasma zone, and only reactive nitrogen species were transformed into reactive peroxynitrite ions. The pH around the cells was determined using an iridium oxide microelectrode. The PAW antialgal mechanism depended on acidic conditions (pH 2.2, at which peroxynitrite can be generated) under which ONOOH penetrated the algal cell membranes, destroying the cells and preventing growth. This practical and sustainable PAW process allows a surprising amount of fertilizer to be generated with an antialgal effect that could be used in various eco-friendly agricultural processes under ambient conditions.

PAW is effective in inactivating microorganisms. We have measured a local pH to reveal the mechanism of algicidal effect in PAW. This is because protons pumped from the cell generate peroxynitrite around the cell to generate an acidic region.     

Splice variants of tissue factor promote monocyte‐endothelial interactions by triggering the expression of cell adhesion molecules via integrin‐mediated signaling

Summary. Background: TF is highly expressed in cancerous and atherosclerotic lesions. Monocyte recruitment is a hallmark of disease progression in these pathological states. Objective: To examine the role of integrin signaling in TF‐dependent recruitment of monocytes by endothelial cells. Methods: The expression of flTF and asTF in cervical cancer and atherosclerotic lesions was examined. Biologic effects of the exposure of primary microvascular endothelial cells (MVEC) to truncated flTF ectodomain (LZ‐TF) and recombinant asTF were assessed. Results: flTF and asTF exhibited nearly identical expression patterns in cancer lesions and lipid‐rich plaques. Tumor lesions, as well as stromal CD68⁺ monocytes/macrophages, expressed both TF forms. Primary MVEC rapidly adhered to asTF and LZ‐TF, and this was completely blocked by anti‐β1 integrin antibody. asTF‐ and LZ‐TF‐treatment of MVEC promoted adhesion of peripheral blood mononuclear cells (PBMCs) under orbital shear conditions and under laminar flow; asTF‐elicited adhesion was more pronounced than that elicited by LZ‐TF. Expression profiling and western blotting revealed a broad activation of cell adhesion molecules (CAMs) in MVEC following asTF treatment including E‐selectin, ICAM‐1 and VCAM‐1. In transwell assays, asTF potentiated PMBC migration through MVEC monolayers by ～3‐fold under MCP‐1 gradient. Conclusions: TF splice variants ligate β1 integrins on MVEC, which induces the expression of CAMs in MVEC and leads to monocyte adhesion and transendothelial migration. asTF appears more potent than flTF in eliciting these effects. Our findings underscore the pathophysiologic significance of non‐proteolytic, integrin‐mediated signaling by the two naturally occurring TF variants in cancer and atherosclerosis.     

Angiotensin II,tissue factor and the thrombotic paradox of hypertension

Tissue factor (TF), the physiologic initiator of blood coagulation, may contribute to the increased risk of thrombotic complications that characterizes arterial hypertension, as suggested by hypertensive animal models showing evidence for TF activation, and clinical studies in hypertensive patients at higher cardiovascular risk with increased circulating levels of TF and thrombogenic microparticles. Angiotensin II stimulates TF expression both in vitro and in vivo, an effect abolished by ACE or angiotensin II receptor inhibition. Moreover, renin–angiotensin system blockers, including aliskiren, a direct renin inhibitor, are able to modulate TF expression in monocytes and vascular endothelial cells activated by inflammatory cytokines. This behavior is suggestive of anti-inflammatory and anti-thrombotic properties of renin–angiotensin system blockers, and is compatible with the possibility that blocking local renin–angiotensin system activation might downregulate TF, thus reducing the risk of ischemic complications in hypertensive patients.     

Mn-based catalysts supported on γ-Al2O3, TiO2 and MCM-41: a comparison for low-temperature NO oxidation with low ratio of O3/NO

Mn-Based catalysts supported on γ-Al₂O₃, TiO₂ and MCM-41 synthesized by an impregnation method were compared to evaluate their NO catalytic oxidation performance with low ratio O₃/NO at low temperature (80–200 °C). Activity tests showed that the participation of O₃ remarkably promoted the NO oxidation. The catalytic oxidation performance of the three catalysts decreased in the following order: Mn/γ-Al₂O₃ > Mn/TiO₂ > Mn/MCM-41, indicating that Mn/γ-Al₂O₃ exhibited the best catalytic activity. In addition, there was a clear synergistic effect between Mn/γ-Al₂O₃ and O₃, followed by Mn/TiO₂ and O₃. The characterization results of XRD, EDS mapping, BET, H₂-TPR, XPS and TG showed that Mn/γ-Al₂O₃ had good manganese dispersion, excellent redox properties, appropriate amounts of coexisting Mn³⁺ and Mn⁴⁺ and abundant chemically adsorbed oxygen, which ensured its good performance. In situ DRIFTS demonstrated the NO adsorption performance on the catalyst surface. As revealed by in situ DRIFTS experiments, the chemically adsorbed oxygen, mainly from the decomposition of O₃, greatly promoted the NO adsorption and the formation of nitrates. The Mn-based catalysts showed stronger adsorption strength than the corresponding pure supports. Due to the abundant adsorption sites provided by pure γ-Al₂O₃, under the interaction of Mn and γ-Al₂O₃, the Mn/γ-Al₂O₃ catalyst exhibited the strongest NO adsorption performance among the three catalysts and produced lots of monodentate nitrates (–O–NO₂) and bidentate nitrates (–O₂NO), which were the vital intermediate species for NO₂ formation. Moreover, the NO–TPD studies also demonstrated that Mn/γ-Al₂O₃ showed the best NO desorption performance among the three catalysts. The good NO adsorption and desorption characteristics of Mn/γ-Al₂O₃ improved its high catalytic activity. In addition, the activity test results also suggested that Mn/γ-Al₂O₃ exhibited good SO₂ tolerance.

The Mn/γ-Al₂O₃ catalyst exhibited excellent performance for NO conversion in the presence of a low ratio of O₃/NO, which was due to the coexistence of Mn³⁺ and Mn⁴⁺ and abundant chemically adsorbed oxygen.     

Insulin inhibits tissue factor expression in monocytes

Summary.  Objectives:  Platelets from healthy subjects are inhibited by insulin but type 2 diabetes mellitus (T2DM) platelets have become insulin-resistant, which might explain their hyperactivity. In the present study we investigated whether monocytes are responsive to insulin. Methods and results:  LPS-induced tissue factor (TF) upregulation was measured in human monocytes and monocytic THP-1 cells in a factor Xa generation assay. Insulin (0.1–100 nmol L⁻¹) induced a dose-dependent inhibition in both cell types and in monocytes 100 nmol L⁻¹ insulin inhibited cytosolic, membrane-bound and microparticle TF by 32 ± 2, 27 ± 3 and 52 ± 4% ( n  = 3). Insulin induced Tyr phosphorylation of the insulin receptor (INS-R) and formation of an INS-R – G_iα₂ complex, suggesting interference with LPS-induced cAMP control. Indeed, insulin interfered with LPS-induced cAMP decrease and TF upregulation in a manner similar to an inhibitor of G_i (pertussis toxin) and agents that raise cAMP (iloprost, forskolin, IBMX) reduced TF upregulation. Although LPS failed to raise cytosolic Ca²⁺, quenching of Ca²⁺ increases (BAPTA-AM) reduced and induction of Ca²⁺ entry (ionophore, P2X7 activation) enhanced upregulation of TF mRNA and procoagulant activity. Insulin interfered with MCP-1-induced Ca²⁺ mobilization but not with ATP-induced Ca²⁺ rises. Conclusions:  Insulin inhibits TF expression in monocytes and monocyte-derived microparticles through interference with G_iα₂-mediated cAMP suppression, which attenuates Ca²⁺-mediated TF synthesis.     

Platelet‐ and erythrocyte‐derived microparticles trigger thrombin generation via factor XIIa

See also Shapiro S, Laffan M. Making contact with microparticles. This issue, pp 1352–4. Summary. Background: The procoagulant properties of microparticles (MPs) are due to the of the presence of phosphatidylserine (PS) and tissue factor (TF) on their surface. The latter has been demonstrated especially on MPs derived from monocytes. Objectives: To investigate the relative contribution of TF and factor (F)XII in initiating coagulation on MPs derived from monocytes, platelets and erythrocytes. Methods: Microparticles were isolated from calcium ionophore‐stimulated platelets, erythrocytes and monocytic THP‐1 cells. MPs were quantified, characterized for cell‐specific antigens and analyzed for TF, PS exposure and their thrombin‐generating potential. Results: The MP number was not proportional to PS exposure and the majority of the MPs exposed PS. TF activity was undetectable on platelet‐ and erythrocyte‐derived MPs (< 1 fm nm ^?1 PS), whereas monocyte‐derived MPs exposed TF (32 fm nm ^?1 PS). Platelet‐, erythrocyte‐ and monocyte‐derived MPs, but not purified phospholipids, initiated thrombin generation in normal plasma in the absence of an external trigger (lag time < 11 min). Deficiency or inhibition of FVII had no effect on thrombin generation induced by platelet‐ and erythrocyte‐derived MPs, but interfered with monocyte MP‐triggered coagulation. Platelet‐ and erythrocyte‐derived MPs completely failed to induce thrombin generation in FXII‐deficient plasma. In contrast, monocyte‐derived MPs induced similar thrombin generation in normal vs. FXII‐deficient plasma. Conclusion: MPs from platelets and erythrocytes not only propagate coagulation by exposing PS but also initiate thrombin generation independently of TF in a FXII‐dependent manner. In contrast, monocyte‐derived MPs trigger coagulation predominantly via TF.     

Acute myocardial infarction with normal coronary arteries during septic shock from Neisseria meningitidis

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (?^·V_A/?^·Q) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and?^·V_A/?^·Qdistributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO₂) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal?^·V_A/?^·Qratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal?^·V_A/?^·Qrelationships.     

Characterization of canine coagulation factor VII and its complex formation with tissue factor: canine–human cross‐species compatibility

Summary. Background: Canine models have been good predictors of efficacy of hemophilia treatments, including recombinant human coagulation factor (F)VIIa (hFVIIa). However, canine FVIIa and tissue factor (TF) have remained incompletely characterized. Objective: To explore canine–human cross‐species FVIIa–TF compatibility in order to strengthen the predictive value of canine models in research on FVIIa and TF. Methods: Canine FVIIa (cFVIIa) and canine TF_(1–217) [cTF_(1–217)] were produced by recombinant techniques, and canine–human cross‐species FVIIa–TF interactions were characterized in vitro. Results: Recombinant cFVIIa and soluble cTF_(1–217) were produced and purified to homogeneity. hFVIIa and cFVIIa bound with comparably high affinities to cTF_(1–217) (K_D = 6.0 ± 0.7 nm and K_D = 6.0 ± 0.3 nm , respectively) and to cell surface‐expressed cTF (K_D = 8.4 ± 0.4 nm and K_D = 7.2 ± 1.2 nm , for ¹²⁵I‐labeled hFVIIa and cFVII, respectively). In contrast, cFVIIa bound to human TF (hTF) with decreased affinity, both in solution and on cell surfaces. The decreased binding resulted in reduced activity of cFVIIa in functional assays with hTF_(1–209). In direct comparison, cFVIIa was more active than hFVIIa, both in the absence and the presence of cognate TF. Conclusion: The present finding that hFVIIa binds to cTF essentially as it does to hTF substantiates the hypothesis that human FVIIa–TF biology can be reliably recapitulated in canine models on administration of hFVIIa to dogs.     

急性冠脉综合征患者血小板和白细胞异常表达组织因子的研究

本研究观察急性冠脉综合征（ACS）患者,稳定性心绞痛（SA）患者及健康对照循环中血小板、血小板白细胞聚集体（PLA）和血小板单核细胞聚集体（PMP）组织因子（TF）的表达情况,并探讨其在ACS发病机制中的作用。收集26例ACS患者,29例SA患者及25名正常人（作为对照组）,外周血标本,分离获得单核细胞及富含血小板血浆,用RT-PCR法分别检测组间单核细胞及血小板TF-mRNA的表达,通过流式细胞仪检测组间血小板、PLA和PMP表达TF的比例。结果表明,ACS组、SA组、正常对照组血小板TF mRNA平均表达水平分别为3.11±0.51、1.88±0.78和0.7±0.10,ACS组单核细胞、血小板TF mRNA表达水平与正常对照组有差异（分别为P=0.03,P=0.05）。ACS组患者血小板表达TF比例明显高于SA组及正常对照组（P=0.02）,3组的TF阳性的PLA百分比（%UR）分别为2.7±0.6、0.8±0.2及0.5±0.1（P=0.001）。ACS组TF阳性的血小板单核细胞百分比（%UR）为2.5±0.6,显著高于SA组的1.2±0.3（P=0.02）及对照组的0.8±0.2（P=0.04）。结论：ACS患者血小板及白细胞高表达TF,促进了血小板的活化、凝血和血栓形成,进一步促进高凝状态。TF促血栓形成和促局部炎症作用,协同血小板和白细胞共同参与ACS的发病,最终与ACS疾病发生发展密切相关。