Correlation of leukocyte interleukin-1 production with the stimulation of prostaglandin and tissue factor synthesis by human umbilical vein endothelial cells

Abstract

Human leukocyte suspensions (neutrophils 80-85%, monocyte 15-20%) were incubated alone or with cultured human umbilical vein endothelial cells. Leukocytes were either directly added to the endothelial cell cultures or separated from them by a 0.4 micron insert filter. Supernatants or cell lysates were obtained at 0.5, 1, 2, and 4 hours of incubation. Supernatants were assayed for the prostacyclin (PGI2) metabolite 6-keto prostaglandin F1 alpha and prostaglandin E2 (PGE2) by radioimmunoassay and for interleukin-1 (IL-1) by the thymocyte co-mitogen assay. Cell lysates were analyzed for cell-associated procoagulant activity (PCA). Co-incubation of endothelial cells with leukocytes stimulated the synthesis of PGI2, PGE2, and PCA. These biochemical changes correlated partially with the release of IL-1 beta. The results suggest that IL-1 released in monocyte neutrophil co-cultures can produce prothrombotic (increased PCA expression) and inflammatory changes (increased synthesis of vasodilatory and permeability enhancing PGI2 and PGE2) in endothelial cells. Neutrophils may represent a source of the released IL-1 and/or may act to stimulate monocyte release of this cytokine and thus play an important role in vascular pathology by a mechanism unrelated to their more direct cytotoxic activity.

Perivascular tissue factor is down-regulated following cutaneous wounding: implications for bleeding in hemophilia

“…9,10 TF expression by several cell types is increased by inflammatory mediators in vitro. [11][12][13] Thrombin triggers secretion of inflammatory mediators and also synergizes with interleukin-1 and tumor necrosis factor to induce endothelial TF. 14 TF messenger RNA in cutaneous tissue is up-regulated immediately following wounding in a mouse model.…”

Animal models of bleeding and tissue repair

“…TF is normally expressed outside the blood vessels [40,41]. A body of in vitro data suggests that products of the coagulation cascade [42] and inflammatory mediators released following injury [43][44][45] promote TF expression. TF messenger RNA in skin samples has also been shown to be upregulated following cutaneous wounding in a mouse model [46].…”

Effects of prostacyclin analogues on human endothelial cell tissue factor expression.

“…10 - 13 Both of these cytokines are secreted by activated monocytes, 1415 suggesting that monocytes can induce or amplify the expression of procoagulant activity by endothelial cells. 16 ' 17 Received February 22, 1993; revision accepted April 19, 1993. From the Miami Heart Research Institute, Miami Beach, Fla.…”