Long‐term incubation with IL‐4 and IL‐10 oppositely modifies procoagulant activity of monocytes and modulates the surface expression of tissue factor and tissue factor pathway inhibitor
Summary Monocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor‐1 (TFPI‐1). A short incubation (<6 h) with interleukin (IL)‐4 and IL‐10, two potent deactivators of monocyte functions, has been shown to modulate the synthesis and expression of TF by mono...
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Published in | British journal of haematology Vol. 131; no. 3; pp. 356 - 365 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Blackwell Science Ltd
01.11.2005
Blackwell Blackwell Publishing Ltd |
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Abstract | Summary
Monocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor‐1 (TFPI‐1). A short incubation (<6 h) with interleukin (IL)‐4 and IL‐10, two potent deactivators of monocyte functions, has been shown to modulate the synthesis and expression of TF by monocytes activated by lipopolysaccharide, but the consequences of longer incubations (up to 96 h) on both TF and TFPI‐1 are unknown. The results of this study showed that adherent monocytes in culture spontaneously expressed TF and TFPI and that prolonged incubation with IL‐10 induced a time‐ and dose‐dependent decrease of monocyte TF synthesis, and an accumulation of TF/TFPI‐1 complexes at the moncyte surface, suggesting a decreased clearance of these complexes. In contrast, IL‐4 induced a time‐ and dose‐dependent increase in TF synthesis, which remained intracytoplasmic, as shown by confocal microscopy. Surprisingly, TF:antigen (Ag) was decreased at the monocyte surface, but the procoagulant activity (PCA) of IL‐4‐treated monocytes was increased, as a result of more pronounced decrease of TFPI‐1:Ag expression than that of TF. In conclusion, prolonged incubation with IL‐4 and IL‐10 oppositely modified PCA of cultured monocytes, and altered TF and TFPI trafficking and clearance. These data explain the respective deleterious or benefit effects of IL‐4 or IL‐10 in atherothrombosis. |
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AbstractList | Summary
Monocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor‐1 (TFPI‐1). A short incubation (<6 h) with interleukin (IL)‐4 and IL‐10, two potent deactivators of monocyte functions, has been shown to modulate the synthesis and expression of TF by monocytes activated by lipopolysaccharide, but the consequences of longer incubations (up to 96 h) on both TF and TFPI‐1 are unknown. The results of this study showed that adherent monocytes in culture spontaneously expressed TF and TFPI and that prolonged incubation with IL‐10 induced a time‐ and dose‐dependent decrease of monocyte TF synthesis, and an accumulation of TF/TFPI‐1 complexes at the moncyte surface, suggesting a decreased clearance of these complexes. In contrast, IL‐4 induced a time‐ and dose‐dependent increase in TF synthesis, which remained intracytoplasmic, as shown by confocal microscopy. Surprisingly, TF:antigen (Ag) was decreased at the monocyte surface, but the procoagulant activity (PCA) of IL‐4‐treated monocytes was increased, as a result of more pronounced decrease of TFPI‐1:Ag expression than that of TF. In conclusion, prolonged incubation with IL‐4 and IL‐10 oppositely modified PCA of cultured monocytes, and altered TF and TFPI trafficking and clearance. These data explain the respective deleterious or benefit effects of IL‐4 or IL‐10 in atherothrombosis. Monocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor-1 (TFPI-1). A short incubation (<6 h) with interleukin (IL)-4 and IL-10, two potent deactivators of monocyte functions, has been shown to modulate the synthesis and expression of TF by monocytes activated by lipopolysaccharide, but the consequences of longer incubations (up to 96 h) on both TF and TFPI-1 are unknown. The results of this study showed that adherent monocytes in culture spontaneously expressed TF and TFPI and that prolonged incubation with IL-10 induced a time- and dose-dependent decrease of monocyte TF synthesis, and an accumulation of TF/TFPI-1 complexes at the moncyte surface, suggesting a decreased clearance of these complexes. In contrast, IL-4 induced a time- and dose-dependent increase in TF synthesis, which remained intracytoplasmic, as shown by confocal microscopy. Surprisingly, TF:antigen (Ag) was decreased at the monocyte surface, but the procoagulant activity (PCA) of IL-4-treated monocytes was increased, as a result of more pronounced decrease of TFPI-1:Ag expression than that of TF. In conclusion, prolonged incubation with IL-4 and IL-10 oppositely modified PCA of cultured monocytes, and altered TF and TFPI trafficking and clearance. These data explain the respective deleterious or benefit effects of IL-4 or IL-10 in atherothrombosis. Monocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor-1 (TFPI-1). A short incubation (<6 h) with interleukin (IL)-4 and IL-10, two potent deactivators of monocyte functions, has been shown to modulate the synthesis and expression of TF by monocytes activated by lipopolysaccharide, but the consequences of longer incubations (up to 96 h) on both TF and TFPI-1 are unknown. The results of this study showed that adherent monocytes in culture spontaneously expressed TF and TFPI and that prolonged incubation with IL-10 induced a time- and dose-dependent decrease of monocyte TF synthesis, and an accumulation of TF/TFPI-1 complexes at the moncyte surface, suggesting a decreased clearance of these complexes. In contrast, IL-4 induced a time- and dose-dependent increase in TF synthesis, which remained intracytoplasmic, as shown by confocal microscopy. Surprisingly, TF:antigen (Ag) was decreased at the monocyte surface, but the procoagulant activity (PCA) of IL-4-treated monocytes was increased, as a result of more pronounced decrease of TFPI-1:Ag expression than that of TF. In conclusion, prolonged incubation with IL-4 and IL-10 oppositely modified PCA of cultured monocytes, and altered TF and TFPI trafficking and clearance. These data explain the respective deleterious or benefit effects of IL-4 or IL-10 in atherothrombosis. |
Author | Paysant, Jérôme Nguyen, Philippe Lenormand, Bernard Soria, Claudine Vannier, Jean‐Pierre Cornillet‐Lefèbvre, Pascale Vasse, Marc Mishal, Zohar |
Author_xml | – sequence: 1 givenname: Jérôme surname: Paysant fullname: Paysant, Jérôme – sequence: 2 givenname: Claudine surname: Soria fullname: Soria, Claudine – sequence: 3 givenname: Pascale surname: Cornillet‐Lefèbvre fullname: Cornillet‐Lefèbvre, Pascale – sequence: 4 givenname: Philippe surname: Nguyen fullname: Nguyen, Philippe – sequence: 5 givenname: Bernard surname: Lenormand fullname: Lenormand, Bernard – sequence: 6 givenname: Zohar surname: Mishal fullname: Mishal, Zohar – sequence: 7 givenname: Jean‐Pierre surname: Vannier fullname: Vannier, Jean‐Pierre – sequence: 8 givenname: Marc surname: Vasse fullname: Vasse, Marc |
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Keywords | interleukin-4 monocytes Kunitz inhibitor Hematology Incubation Monocyte Cytokine Tissue factor Procoagulant activity atherothrombosis Long term interleukin-10 Interleukin 4 Interleukin 10 tissue factor pathway inhibitor-1 Tissue factor pathway inhibitor |
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Monocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor‐1 (TFPI‐1). A short incubation (<6 h) with... Monocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor-1 (TFPI-1). A short incubation (<6 h) with interleukin... Monocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor-1 (TFPI-1). A short incubation (<6 h) with interleukin... |
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SubjectTerms | Antibodies, Monoclonal - immunology atherothrombosis Biological and medical sciences Blood Coagulation Factors - metabolism Cells, Cultured Cytoplasm - metabolism Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay - methods Gene Expression Hematologic and hematopoietic diseases Hematology Humans Interleukin-10 - pharmacology Interleukin-4 - pharmacology interleukin‐10 interleukin‐4 Lipoproteins - antagonists & inhibitors Lipoproteins - genetics Lipoproteins - metabolism Medical sciences Microscopy, Confocal monocytes Monocytes - drug effects Monocytes - metabolism Reverse Transcriptase Polymerase Chain Reaction - methods RNA, Messenger - genetics Thromboplastin - genetics Thromboplastin - metabolism Time Factors tissue factor tissue factor pathway inhibitor‐1 |
Title | Long‐term incubation with IL‐4 and IL‐10 oppositely modifies procoagulant activity of monocytes and modulates the surface expression of tissue factor and tissue factor pathway inhibitor |
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