Induction of tissue factor-like activity of human monoblastic leukemia cell line by tumor necrosis factor-alpha.
Cell lysates of the human monoblastic leukemia cell line, THP-1, have procoagulant activity (PCA) that is Ca++-dependent and not demonstrable in either Factor VII-, or Factor X-deficient plasma. The PCA of THP-1 cells was enhanced by human recombinant tumor necrosis factor-alpha (TNF-alpha) up to five fold. There was a dose-dependent increase in PCA when THP-1 cells were cultured with concentrations of TNF-alpha, up to 10 U/ml. PCA of cell lysates or whole cell preparations was measured in comparison to a rabbit brain thromboplastin standard. The effect of TNF-alpha was enhanced by recombinant human interferon-gamma (IFN-gamma). Cycloheximide inhibited the induction of PCA by THP-1 cells, which shows that the protein synthesis is essential to mediate the effect of TNF-alpha. THP-1 cells and U937 cells bound 125I-labeled TNF specifically. The numbers of receptors per cell were found to be 1,890 and 1,550 for THP-1 and U937 cells, respectively. Other lymphoid and myeloblastic leukemia cell lines examined did not have TNF receptors, indicating that the effect of TNF-alpha is mediated by the receptors on the cell surface.
Tanaka
M
M
Nagoya National Hospital, Hematological Disease Center, Japan.
D001779:Blood Coagulation Factors / Q000096:biosynthesis; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D013925:Thromboplastin / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001779:Blood Coagulation Factors; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C045071:leukocyte procoagulant activity; D013925:Thromboplastin