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Membrane thrombomodulin (TM) is a very efficient natural anti-thrombin glycoprotein with anticoagulant properties expressed on endothelial cell surface. Circulating plasmatic thrombomodulin (TMp) detected by enzyme immunoassay in plasma is considered as a cell marker of endothelial injury. The TMp levels are increased in many conditions (diabetes mellitus, atheromatous disease...). In cases of collagen vascular diseases, where vascular endothelium damage is suspected, TMp is increased particularly in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). It is noteworthy that the TMp level is correlated with disease activity. Since TMp is a non specific marker of endothelial damage, it may be of interest as a useful marker for the supervision of these diseases. Further studies are needed on larger series. TMp level change during spontaneous evolution or under treatment will help determine wether TMp is a predictor and prognostic marker of these systemic diseases.

P-selectin is an endothelial adhesion molecule involved in the initial step of the neutrophil recruitment. We investigated the effect of hypoxia (95% N2, 5% CO2) and of hypoxia-reoxygenation (95% air, 5% CO2) on the expression of P-selectin by human umbilical vein endothelial cells (HUVEC). P-selectin expression was detected by immunolabelling and quantified by flow cytometric analysis. Our data indicate that hypoxia induces an increase in P-selectin expression with a maximum reached after 90 minutes. A hypoxic exposure of 90 minutes results in a highly significant increase compared to normoxia (p < 0.001, n=13). Furthermore, when a reoxygenation period follows 90 minutes of hypoxia, the initially elevated levels of P-selectin are dramatically enhanced with a maximum obtained after 60 minutes of reoxygenation.

Thrombomodulin is a membrane glycoprotein expressed by endothelium and is a receptor for thrombin. The thrombin-thrombomodulin complex inactivates the procoagulant activity of thrombin and catalyzes activation of protein C(1). The decrease in thrombomodulin expression at the surface of the vascular endothelium may contribute to the development of thrombosis. In vitro studies have shown that cytokines (TNF, IL-1) or endotoxins down regulate thrombomodulin expression (2, 3, 4) whereas histamine (5), retinoic acid (6) and cAMP analogs (7, 8) increase its expression. Hypoxia is frequently related to disorders of the vascular system such as atheromatous arterial disease and venous insufficiency (9). Clinically, hypoxia induces an increase in vascular permeability (10) and a prothrombotic tendency (12). In vitro, it has been demonstrated that hypoxia is able to modify endothelial properties. In effect, hypoxia has been shown to down regulate thrombornodulin expression on bovine arterial endothelial cells (BAEC) and microvascular endothelial cells (11, 13, 14). Moreover, it has been demonstrated that hypoxia decreases endothelial cell barrier function by lowering cAMP levels (15). cAMP is the major up regulator of thrombomodulin expression, so we investigated the effect of agents able to increase cAMP levels on membrane thrombomodulin expression in hypoxic conditions on HUVEC

Resume Introduction. — Le facteur de transcription NF-κB est un regulateur essentiel des ganes impliques dans la reponse a l’infection, a l’inflammation et au stress. Il a ete decrit comme une proteine fixee a une region specifique de l’ADN, constituee de dix paires de bases, activatrice du gane de la chaine legare κ des lymphocytes B. Actualites et points forts. — NF-κB est habituellement present dans le cytoplasme de la cellule fixee a une proteine inhibitrice appelee IκB. Le signal de localisation nucleaire (NLS) du NF-κB correspond a une courte sequence d’acides amines impliques dans le transport vers le noyau. Lors de l’activation de NF-κB, la proteine IκB est dissociee et degradee du complexe NF-κB. NF-κB migre alors vers le noyau et se fixe au niveau de son site ADN-specifique. La repression de l’expression du gane dependant de NF-κB serait un des elements majeurs de l’immunodepression induite par les glucocorticoides. Perspectives et projets. — Au niveau d’un site inflammatoire, les cellules endotheliales expriment de nombreux ganes sous le controle du facteur nucleaire NF-κB. Ce facteur de transcription, en presence de ses inhibiteurs, est au centre d’un systame d’autoregulation qui peut etre active par de nombreux stimuli au cours de diverses situations pathologiques vasculaires. NF-κB est ainsi un candidat serieux pour un nouveau type de traitement anti-inflammatoire.

Introduction Some viral infections are associated with deep venous thrombosis. We report a case of deep venous thrombosis in an adult with varicella. He had neither known predisposing factors for thrombosis nor thrombophilia. Exegesis Transient significant level of antiphospholipid antibodies and lupus circulating anticoagulant were observed. There was no evidence of thrombophilia. Deep venous thrombosis has been mostly associated with varicella in children. A transient protein S deficiency was present in almost all cases, though it was sometimes related to an anti-protein S antibody. This association is exceptional in adults. Some viruses such as herpesvirus and HIV are responsible for endothelium dysfunction, but this is still unclear in the case of varicella-zoster virus. Conclusion In our observation, endothelium activation or antiphospholipid antibodies might be responsible for thrombosis.

Variations of plasma thrombomodulin levels, which is a putative marker of endothelial damage, were measured in 23 cases of systemic lupus erythematosus (without antiphospholipids and/or lupus anticoagulants) and in 7 dermatopolymyositis. This parameter was significantly increased in dermatopolymyositis suggesting the involvement of ischemia in endothelium injury. No change in plasma thrombomodulin levels was observed in patients with systemic lupus erythematosus.

Plasma thrombomodulin (TMp) is proned as a marker of endothelial cell domage. Significantly elevated levels were found in patients with atherosclerosis. Furthermore a positive correlation was pointed out between TMp and prostacyclin (PG12) and tissue-type plasminogen activator (t-PA) which are markers of endothelial cells activation.