Monocyte IL-10 produced in response to lipopolysaccharide modulates thrombin generation by inhibiting tissue factor expression and release of active tissue factor-bound microparticles

Stéphane Poitevin; Eva Cochery-Nouvellon; Annick Dupont; Philippe Nguyen

doi:10.1160/TH06-11-0622

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(04): 598-607
DOI: 10.1160/TH06-11-0622

Platelets and Blood Cells

Schattauer GmbH

Monocyte IL-10 produced in response to lipopolysaccharide modulates thrombin generation by inhibiting tissue factor expression and release of active tissue factor-bound microparticles

Stéphane Poitevin

¹Laboratory of Hematology, CHU Robert Debré and UPRES EA3796, Faculty of Medicine, University of Reims-Champagne Ardenne, Reims, France

,

Eva Cochery-Nouvellon

¹Laboratory of Hematology, CHU Robert Debré and UPRES EA3796, Faculty of Medicine, University of Reims-Champagne Ardenne, Reims, France

,

Annick Dupont

¹Laboratory of Hematology, CHU Robert Debré and UPRES EA3796, Faculty of Medicine, University of Reims-Champagne Ardenne, Reims, France

,

Philippe Nguyen

¹Laboratory of Hematology, CHU Robert Debré and UPRES EA3796, Faculty of Medicine, University of Reims-Champagne Ardenne, Reims, France

› Author Affiliations

Abstract

Summary

Lipopolysaccharide (LPS)-stimulated monocytes are known to have a procoagulant effect. This property is currently explained by the fact that monocytes, in response to LPS, can express tissue factor (TF) and undergo a process of membrane microvesiculation. Interleukin-10 (IL-10) has been shown to downregulate TF expression and inhibit procoagulant activity (PCA). In order to further characterize the inhibitory effect of IL-10 on LPS-induced PCA, we used the integrated system of analysis of kinetics of thrombin generation in normal plasma (thrombinography). For this, we developed an original method of elutriation allowing to obtain a highly purified monocyte preparation, under endotoxin-free conditions. Thrombin generation was measured using a highly sensitive and specific fluorogenic method which we adapted to inhibit the contact factor pathway. Results show that recombinant human IL-10 decreased the kinetics of thrombin generation in a dose-dependent manner. Furthermore, the inhibition of endogenous IL-10 released by monocytes in response to LPS is associated with an increase in the kinetics of thrombin generation. We demonstrated that this effect was a consequence of the up-regulation of TF expression and TF-bound microparticle release. In conclusion, we report that IL-10 can regulate thrombin generation in conditions close to physiology as allowed by thrombinography, and that endogenous IL-10 regulates TF expression and release of active TF-bound microparticles by a negative feed back loop through IL-10 receptor α

Keywords

microparticles - Interleukin-10 - monocytes - thrombin generation - tissue factor

Full Text

References

References
1 Glauser MP, Zanetti G, Baumgartner JD. et al. Septic shock: pathogenesis. Lancet 1991; 338: 732-736.
2 de Waal Malefyt R, Abrams J, Bennett B. et al. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174: 1209-1220.
3 Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med 1989; 170: 2081-2095.
4 Moore KW, de Waal Malefyt R, Coffman RL. et al. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 2001; 19: 683-765.
5 Esmon CT. The interactions between inflammation and coagulation. Br J Haematol 2005; 131: 417-430.
6 Fair DS, MacDonald MJ. Cooperative interaction between factor VII and cell surface-expressed tissue factor. J Biol Chem 1987; 262: 11692-11698.
7 Jungi TW, Brcic M, Eperon S. et al. Transforming growth factor-beta and interleukin-10, but not interleukin- 4, down-regulate procoagulant activity and tissue factor expression in human monocyte-derived macrophages. Thromb Res 1994; 76: 463-474.
8 Lindmark E, Tenno T, Chen J. et al. IL-10 inhibits LPS-induced human monocyte tissue factor expression in whole blood. Br J Haematol 1998; 102: 597-604.
9 Osnes LT, Westvik AB, Joo GB, et al.. Inhibition of IL-1 induced tissue factor (TF) synthesis and procoagulant activity (PCA) in purified human monocytes by IL-4, IL-10 and IL-13. Cytokine 1996; 8: 822-827.
10 Pradier O, Gerard C, Delvaux A. et al. Interleukin- 10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide. Eur J Immunol 1993; 23: 2700-2703.
11 Shet AS, Aras O, Gupta K. et al. Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood 2003; 102: 2678-2683.
12 Freyssinet JM. Cellular microparticles: what are they bad or good for?. J Thromb Haemost 2003; 1: 1655-1662.
13 Simak J, Gelderman MP. Cell membrane microparticles in blood and blood products: potentially pathogenic agents and diagnostic markers. Transfus Med Rev 2006; 20: 1-26.
14 Nguyen P, Broussas M, Cornillet-Lefebvre P. et al. Coexpression of tissue factor and tissue factor pathway inhibitor by human monocytes purified by leukapheresis and elutriation. Response of nonadherent cells to lipopolysaccharide. Transfusion 1999; 39: 975-982.
15 Hemker HC, Giesen P, AlDieri R. et al. The calibrated automated thrombogram (CAT): a universal routine test for hyper- and hypocoagulability. Pathophysiol Haemost Thromb 2002; 32: 249-253.
16 Hemker HC, Giesen PL, Ramjee M. et al. The thrombogram: monitoring thrombin generation in platelet- rich plasma. Thromb Haemost 2000; 83: 589-591.
17 Tanaka KA, Szlam F, Katori N. et al. Evaluation of a novel kallikrein inhibitor on hemostatic activation in vitro. Thromb Res 2004; 113: 333-339.
18 Abid Hussein MN, Meesters EW, Osmanovic N. et al. Antigenic characterization of endothelial cell-derived microparticles and their detection ex vivo. J Thromb Haemost 2003; 1: 2434-2443.
19 Satta N, Toti F, Feugeas O. et al. Monocyte vesiculation is a possible mechanism for dissemination of membrane-associated procoagulant activities and adhesion molecules after stimulation by lipopolysaccharide. J Immunol 1994; 153: 3245-3255.
20 Byrne A, Reen DJ. Lipopolysaccharide induces rapid production of IL-10 by monocytes in the presence of apoptotic neutrophils. J Immunol 2002; 168: 1968-1977.
21 Ralph P, Nakoinz I, Sampson-Johannes A. et al. IL-10, T lymphocyte inhibitor of human blood cell production of IL-1 and tumor necrosis factor. J Immunol 1992; 148: 808-814.
22 Thompson-Snipes L, Dhar V, Bond MW. et al. Interleukin 10: a novel stimulatory factor for mast cells and their progenitors. J Exp Med 1991; 173: 507-510.
23 Brand K, Fowler BJ, Edgington TS. et al. Tissue factor mRNA in THP-1 monocytic cells is regulated at both transcriptional and posttranscriptional levels in response to lipopolysaccharide. Mol Cell Biol 1991; 11: 4732-4738.
24 Hall AJ, Vos HL, Bertina RM. Lipopolysaccharide induction of tissue factor in THP-1 cells involves Jun protein phosphorylation and nuclear factor kappaB nuclear translocation. J Biol Chem 1999; 274: 376-383.
25 Norris LA, Weldon S, Nugent A. et al. LPS induced tissue factor expression in the THP-1 monocyte cell line is attenuated by conjugated linoleic acid. Thromb Res 2006; 117: 475-480.
26 Cadroy Y, Dupouy D, Boneu B. et al. Polymorphonuclear leukocytes modulate tissue factor production by mononuclear cells: role of reactive oxygen species. J Immunol 2000; 164: 3822-3828.
27 Eggesbo JB, Hjermann I, Ovstebo R. et al. LPS induced procoagulant activity and plasminogen activator activity in mononuclear cells from persons with high or low levels of HDL lipoprotein. Thromb Res 1995; 77: 441-452.
28 Walsh JD, Geczy CL. Discordant expression of tissue factor antigen and procoagulant activity on human monocytes activated with LPS and low dose cycloheximide. Thromb Haemost 1991; 66: 552-558.
29 Meisel SR, Shechter M, Xu XP. et al. Platelet-induced expression of tissue factor procoagulant activity in freshly isolated human mononuclear cells: implications for experimental use. Clin Lab Haematol 2003; 25: 321-325.
30 Aras O, Shet A, Bach RR. et al. Induction of microparticle- and cell-associated intravascular tissue factor in human endotoxemia. Blood 2004; 103: 4545-4553.
31 Eskdale J, Gallagher G, Verweij CL. et al. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc Natl Acad Sci USA 1998; 95: 9465-9470.
32 Westendorp RG, Langermans JA, Huizinga TW. et al. Genetic influence on cytokine production in meningococcal disease. Lancet 1997; 349: 1912-1913.
33 Bogdanov VY, Balasubramanian V, Hathcock J. et al. Alternatively spliced human tissue factor: a circulating, soluble, thrombogenic protein. Nat Med 2003; 9: 458-462.
34 Osterud B, Bjorklid E. Sources of tissue factor. Semin Thromb Hemost 2006; 32: 11-23.
35 Censarek P, Bobbe A, Grandoch M. et al. Alternatively spliced human tissue factor (asHTF) is not procoagulant. Thromb Haemost 2007; 97: 11-14.
36 Mackman N. Alternatively spliced tissue factor – one cut too many?. Thromb Haemost 2007; 97: 5-8.
37 Arai T, Hiromatsu K, Nishimura H. et al. Endogenous interleukin 10 prevents apoptosis in macrophages during Salmonella infection. Biochem Biophys Res Commun 1995; 213: 600-607.
38 Eslick J, Scatizzi JC, Albee L. et al. IL-4 and IL-10 inhibition of spontaneous monocyte apoptosis is associated with Flip upregulation. Inflammation 2004; 28: 139-145.
39 Ernofsson M, Tenno T, Siegbahn A. Inhibition of tissue factor surface expression in human peripheral blood monocytes exposed to cytokines. Br J Haematol 1996; 95: 249-257.
40 Kamimura M, Viedt C, Dalpke A. et al. Interleukin- 10 suppresses tissue factor expression in lipopolysaccharide- stimulated macrophages via inhibition of Egr-1 and a serum response element/MEK-ERK1/2 pathway. Circ Res 2005; 97: 305-313.
41 Bhattacharyya S, Sen P, Wallet M. et al. Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of IkB kinase activity. Blood 2004; 104: 1100-1109.
42 Denys A, Udalova IA, Smith C. et al. Evidence for a dual mechanism for IL-10 suppression of TNF-alpha production that does not involve inhibition of p38 mitogen- activated protein kinase or NF-kappa B in primary human macrophages. J Immunol 2002; 168: 4837-4845.
43 Mallat Z, Hugel B, Ohan J. et al. Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques: a role for apoptosis in plaque thrombogenicity. Circulation 1999; 99: 348-353.
44 Matsumoto N, Nomura S, Kamihata H. et al. Increased level of oxidized LDL-dependent monocytederived microparticles in acute coronary syndrome. Thromb Haemost 2004; 91: 146-154.
45 Cochery-Nouvellon E, Vitry F, Cornillet-Lefebvre P. et al. Interleukin-10 promoter polymorphism and venous thrombosis. A case-control study. Thromb Haemost 2006; 96: 24-28.
46 Kamali-Sarvestani E, Zolghadri J, Gharesi-Fard B. et al. Cytokine gene polymorphisms and susceptibility to recurrent pregnancy loss in Iranian women. J Reprod Immunol 2005; 65: 171-178.
47 Zammiti W, Mtiraoui N, Cochery-Nouvellon E. et al. Association of –592C/A, –819C/T and –1082A/G interleukin-10 promoter polymorphisms with idiopathic recurrent spontaneous abortion. Mol Hum Reprod 2006; 12: 771-776.