Epidermal growth factor enhances lipopolysaccharide-induced procoagulant activity on the cell surface of endothelial...

Endotoxin [lipopolysaccharide (LPS)] and some cytokines are known to induce tissue factors with the expression of procoagulant activity (PCA) on the cell surface of endothelial cells. We established a modified quantitative procedure for PCA expressed on the cell surface, and studied the effects of serum and epidermal growth factor (EGF) on the LPS-induced activation of PCA on cultured human umbilical vein endothelial cells. Meanwhile, human umbilical cord serum elevated PCA more than either fetal bovine serum (FBS) or human adult serum. Generally, the existence of LPS raises the concentration of EGF in the blood, since monocytes and other types of cells express EGF and release it into the vessel by LPS stimulation. Although 10 ng/ml EGF did not induce PCA even in the presence of 10% FBS, it enhanced LPS-induced PCA under the same conditions. In the presence of 10% FBS, PCA induced both by LPS alone and by LPS + EGF was reduced the same amount by the protein kinase C (PKC) inhibitors H7 and H8. These results suggest that the serum contains some cofactor other than EGF, and that EGF enhanced this LPS-induced PCA independent of the cofactor through PKC-involved signaling.