Cultured human endothelial cells generate tissue factor in response to endotoxin.

Abstract

A B S T R A C T Bacterial infection is associated with disseminated intravascular coagulation and fibrin de-position in the microcirculation; the mechanism of these effects in humans is still unclear. We 28 March 1983. were observed in the absence of endothelial damage, as shown by phase-contrast mnicroscopy and lack of 51Cr release. These data coul(d contribute to elucidate the pathogenesis of vascular complications associated with endotoxemia in man.INTRODUCTIO'N Endotoxin-producing bacte ria cause disseminated intravascular coagulation (D[IC),' shock, and ultimate death of an estimated 25.% of patients with bloodstream infections (1,2). The mechanism of endotoxin action in man is still unclear and difficult to study. In animals endotoxin induce s injury of endothelial cells (EC) and this is thought to play an important role in blood clotting activation (3, 4).We describe here exp)eriments indicating that endotoxin induces the gelieration of tissue factor procoagulant by cultured inuman EC. This hitherto undescribed effect of endQtoxin could play a key role in the generation and deposition of fibrin in blood vessels.

Glomerular procoagulant activity in human proliferative glomerulonephritis.

“…Other inflammatory cells such as neutrophils and lymphocytes do not express PCA (16,17). Intrinsic glomerular cells have not been shown to express PCA, although under certain culture conditions endothelial cells may express low levels of tissue factor that can be augmented by interleukin 1 (39,40). Therefore, the potential exists for macrophages to also augment glomerular PCA by the effects of interleukin 1 on glomerular endothelial cells.…”

Measles Virus Induction of Human Endothelial Cell Tissue Factor Procoagulant Activity in Vitro

“…It was possible that contamination with endotoxin might have been responsible for the induction of PCA by measles virus, since LPS is known to have this capacity (Colucci et al, 1983). However, LPS was not detected in the media or cell supernatants as determined by the limulus assay, which has a lower limit of detection of 4.2 pg/ml.…”

Defibrotide reduces procoagulant activity and increases fibrinolytic properties of endothelial cells

“…In our experiments, a high LPS dose was used according to a standard procedure utilized in our laboratory and established on the basis of published studies. [39][40][41] However, lower LPS doses (1.0 and 0.1 mg/ml) fully activated both EC types, and DF was equally active in counteracting the procoagulant and antifibrinolytic actions induced by all of these LPS doses (data not shown). TF is the major activator of blood coagulation.…”