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.

Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells.

“…Endotoxin has been reported to induce PCA in primary HEC cultures (3,4). We confirmed this observation and found a similar result in serially passaged HEC.…”

“…1 b). Activity peaked between 3 and 6 h and declined to near basal levels by 24 h. Addition of fresh IL-1 at 24 h gave negligible restimulation by 28 h, suggesting that the HEC had become Endotoxin has been reported to induce PCA in primary HEC cultures (3,4). We confirmed this observation and found a similar result in serially passaged HEC.…”

Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells.

“…Endotoxin has been reported to induce PCA in primary HEC cultures (3,4). We confirmed this observation and found a similar result in serially passaged HEC.…”

“…1 b). Activity peaked between 3 and 6 h and declined to near basal levels by 24 h. Addition of fresh IL-1 at 24 h gave negligible restimulation by 28 h, suggesting that the HEC had become Endotoxin has been reported to induce PCA in primary HEC cultures (3,4). We confirmed this observation and found a similar result in serially passaged HEC.…”

Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro.

“…The time course of tissue factor expression is identical to that observed in previous studies (15)(16)(17)(18) with maximal expression at 6 h and subsequent return to baseline by 24 h. We report that endotoxin-stimulated tissue factor expression is accompanied by a sustained dose-dependent suppression of thrombomodulin activity that occurs at the same threshold endotoxin concentration that promotes tissue factor expression. Other investigators have recently observed that thrombomodulin expression declines after exposure to other inflammatory mediators, including interleukin 1 (38) and tumor necrosis factor (TNF) (39).…”

Echinomycin Suppresses the Pyrogenic Effects of Endotoxin and Interleukin- lβ in Human Endothelial Cells and Peripheral Blood Mononuclear Cells

“…In this report, we have confirmed that LPS and IL-ip act on human vascular endothelium and mononuclear cells to induce the expression of tissue factor. This effect, like that previously reported (15)(16)(17)(18)(19)(20), was found to be concentration-dependent, time-dependent and reversible (not shown). It is noteworthy that after incubation with the highest doses of LPS, human PBMC exhibited higher maximal levels of TF, compared to LPS-stimulated HUVEC.…”

Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells.

“…Endotoxin has been reported to induce PCA in primary HEC cultures (3,4). We confirmed this observation and found a similar result in serially passaged HEC.…”

“…1 b). Activity peaked between 3 and 6 h and declined to near basal levels by 24 h. Addition of fresh IL-1 at 24 h gave negligible restimulation by 28 h, suggesting that the HEC had become Endotoxin has been reported to induce PCA in primary HEC cultures (3,4). We confirmed this observation and found a similar result in serially passaged HEC.…”

Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro.

“…The time course of tissue factor expression is identical to that observed in previous studies (15)(16)(17)(18) with maximal expression at 6 h and subsequent return to baseline by 24 h. We report that endotoxin-stimulated tissue factor expression is accompanied by a sustained dose-dependent suppression of thrombomodulin activity that occurs at the same threshold endotoxin concentration that promotes tissue factor expression. Other investigators have recently observed that thrombomodulin expression declines after exposure to other inflammatory mediators, including interleukin 1 (38) and tumor necrosis factor (TNF) (39).…”

Echinomycin Suppresses the Pyrogenic Effects of Endotoxin and Interleukin- lβ in Human Endothelial Cells and Peripheral Blood Mononuclear Cells

“…In this report, we have confirmed that LPS and IL-ip act on human vascular endothelium and mononuclear cells to induce the expression of tissue factor. This effect, like that previously reported (15)(16)(17)(18)(19)(20), was found to be concentration-dependent, time-dependent and reversible (not shown). It is noteworthy that after incubation with the highest doses of LPS, human PBMC exhibited higher maximal levels of TF, compared to LPS-stimulated HUVEC.…”

Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells.

“…Endotoxin has been reported to induce PCA in primary HEC cultures (3,4). We confirmed this observation and found a similar result in serially passaged HEC.…”

“…1 b). Activity peaked between 3 and 6 h and declined to near basal levels by 24 h. Addition of fresh IL-1 at 24 h gave negligible restimulation by 28 h, suggesting that the HEC had become Endotoxin has been reported to induce PCA in primary HEC cultures (3,4). We confirmed this observation and found a similar result in serially passaged HEC.…”

Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro.

“…The time course of tissue factor expression is identical to that observed in previous studies (15)(16)(17)(18) with maximal expression at 6 h and subsequent return to baseline by 24 h. We report that endotoxin-stimulated tissue factor expression is accompanied by a sustained dose-dependent suppression of thrombomodulin activity that occurs at the same threshold endotoxin concentration that promotes tissue factor expression. Other investigators have recently observed that thrombomodulin expression declines after exposure to other inflammatory mediators, including interleukin 1 (38) and tumor necrosis factor (TNF) (39).…”

Echinomycin Suppresses the Pyrogenic Effects of Endotoxin and Interleukin- lβ in Human Endothelial Cells and Peripheral Blood Mononuclear Cells

“…In this report, we have confirmed that LPS and IL-ip act on human vascular endothelium and mononuclear cells to induce the expression of tissue factor. This effect, like that previously reported (15)(16)(17)(18)(19)(20), was found to be concentration-dependent, time-dependent and reversible (not shown). It is noteworthy that after incubation with the highest doses of LPS, human PBMC exhibited higher maximal levels of TF, compared to LPS-stimulated HUVEC.…”