Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity.
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/5x10(5) cells after exposure to 100 ng/L IL-6 for 4 hours and by 6.6-fold to 27 +/- 4 mU/5x10(5) 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.
Neumann
F J
FJ
Deutsches Herzzentrum München, Technischen Universität München, Germany. neumann@dhm.mhn.de
Ott
I
I
Marx
N
N
Luther
T
T
Kenngott
S
S
Gawaz
M
M
Kotzsch
M
M
Schömig
A
A
D001779:Blood Coagulation Factors / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000648:ultrastructure; D011994:Recombinant Proteins; D013925:Thromboplastin / Q000378:metabolism*
D001779:Blood Coagulation Factors; D015850:Interleukin-6; D016209:Interleukin-8; D011994:Recombinant Proteins; C045071:leukocyte procoagulant activity; D013925:Thromboplastin