Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3399-3405
© 1997 American Heart Association, Inc.
Articles |
Effect of Human Recombinant Interleukin-6 and Interleukin-8 on Monocyte Procoagulant Activity
From the Deutsches Herzzentrum München und 1. Medizinische Klinik der Technischen Universität München, and the Institut für Pathologie der Technischen Universität Dresden (T.L., M.K.), Germany.
Correspondence to Prof Dr Franz-Josef Neumann, Deutsches Herzzentrum München und 1. Medizinische Klinik der Technischen Universität, Lazarettstr 36, 80636 München, Germany. E-mail neumann{at}dhm.mhn.de
Abstract Interleukin (IL)-6 and IL-8 are important regulators of inflammatory responses in myocardial infarction. Induction of monocyte procoagulant activity (PCA) by these cytokines could present a mechanism that links inflammatory responses to thrombotic events. We therefore investigated the effect of IL-6 and IL-8 on monocyte tissue factor (TF) expression. Recombinant human IL-6 and IL-8 caused a time- and dose-dependent increase in PCA (recalcification time) of monocytic U937 cells and of mononuclear leukocytes. Using blocking anti-TF monoclonal antibodies and factor VII–deficient control plasma, this PCA was shown to be TF dependent. Compared with unstimulated cells, mononuclear cell PCA increased by 4.5-fold to 17±2 mU/5x105 cells after exposure to 100 ng/L IL-6 for 4 hours and by 6.6-fold to 27±4 mU/5x105 cells after exposure to IL-8 under the same conditions. Northern blot analysis showed an increase in TF mRNA after stimulation with IL-6 or IL-8 for 2 hours, and after 4 hours an increase in cellular TF protein content was found by immunoassay. Flow cytometry demonstrated that IL-6 and IL-8 induced an increase in TF surface expression on monocytes. Thus, IL-6 and IL-8 induce monocyte PCA by increasing mRNA, protein content, and surface expression of TF.
Key Words: tissue factor • interleukins • monocytes
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