RSS-Feed abonnieren
DOI: 10.1055/s-0037-1613406
Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated by thrombin in human monocytes and THP-1 cells in vitro and in pregnant subjects in vivo
Financial support: The research was funded, in part, by a grant from The Laurence Scott Trust. The sponsors of the study had no role in the study design, data collection, analysis or writing of the report.Publikationsverlauf
Received
09. September 2002
Accepted after revision
24. März 2003
Publikationsdatum:
08. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200306/lookinside/thumbnails/10-1055-s-0037-1613406-1.jpg)
Summary
Monocytes play a pivotal role in both the inflammatory and coagulation responses, which may be mediated through a variety of adhesion molecules on the cell surface, including intercellular adhesion molecule-1 (ICAM-1). Monocytes also possess thrombin receptors. In the current study, we have demonstrated that thrombin can upregulate ICAM-1 mRNA and induce ICAM-1 expression on the monocyte in vitro and that, in vivo, higher monocyte ICAM-1 expression is observed in pregnancy (which is characterised by a physiological increase in thrombin generation). In pregnant subjects, a positive correlation between monocyte ICAM-1 expression and a number of markers of vascular/thrombotic disease (including blood group, acquired activated protein C resistance and non-fasting plasma triglyceride levels) was observed. We also observed a significant relationship between monocyte ICAM-1 expression and soluble plasma ICAM-1 levels, which would be consistent with a contribution of monocytic ICAM-1 to the levels of free ICAM-1 observed in plasma during pregnancy.
Consistent with a role in fibrinogen binding, our preliminary in vivo results suggest that monocyte ICAM-1 expression may be a useful marker of the thrombotic/inflammatory response, although further work is required to assess the relationship of monocyte ICAM-1 expression in thrombotic disorders.
-
References
- 1 Ott I, Andrassy M, Zieglgansberger D. et al. Regulation of monocyte procoagulant activity in acute myocardial infarction: role of tissue factor and tissue factor pathway inhibitor-1. Blood 2001; 97: 3721-6.
- 2 Li A, Chang AC, Peer GT. et al. Recombinant tissue factor pathway inhibitor enhances the binding of factor Xa to human monocytes. Thromb Haemost 2001; 85: 830-6.
- 3 Ritchie H, Robbie LA, Kinghorn S. et al. Monocyte plasminogen activator inhibitor 2 (PAI-2) inhibits u-PA-mediated fibrin clot lysis and is cross-linked to fibrin. Thromb Haemost 1999; 81: 96-103.
- 4 Bar-Shavit R, Hruska KA, Kahn AJ. et al. Thrombin chemotactic stimulation of HL-60 cells: studies on thrombin responsiveness as a function of differentiation. J Cell Physiol 1987; 131: 255-61.
- 5 Hoffman MC, Church F.C. Response of blood leukocytes to thrombin receptor peptides. J Leuk Biol 1993; 54: 145-51.
- 6 Ritchie HJ, Jamieson A, Booth NA. Thrombin modulates synthesis of plasminogen activator inhibitor type 2 by human peripheral blood monocytes. Blood 1995; 86: 3428-35.
- 7 Clark P, Brennand J, Conkie JA. et al. Activated protein C sensitivity, protein C, protein S and coagulation in normal pregnancy. Thromb Haemost 1998; 79: 1166-70.
- 8 Clark P, Greer I, Walker I. Interaction of the protein C/protein S anticoagulant system, the endothelium and pregnancy. Blood Reviews 1999; 13: 127-46.
- 9 Dougherty GJ, Murdoch S, Hogg N. The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of an immune response. Eur J Immunol 1988; 18: 35-9.
- 10 Altieri DC, Duperray A, Plescia J. et al. Structural recognition of a novel fibrinogen gamma chain sequence (117-133) by intercellular adhesion molecule-1 mediates leukocyte-endothelium interaction. J Biol Chem 1995; 270: 696-9.
- 11 Arefieva T, Krasnikova T. Monocyte cell adhesion to intact and plasmin-modified fibrino-gen: possible involvement of Mac-1 (CD11b/ CD18) and ICAM-1 (CD54). J Cell Physiol 2001; 188: 403-9.
- 12 Herrick S, Blanc-Rude O, Gray A. et al. Fibrinogen. Int J Biochem 1999; 31: 741-6.
- 13 Smith E, Thompson W. Fibrin as a cofactor in atherogenesis. Thromb Res 1994; 73: 1-19.
- 14 Kaplanski G, Marin V, Fabrigoule M. et al. Thrombin-activated human endothelial cells support monocyte adhesion in vitro following expression of intercellular adhesion molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106). Blood 1998; 92: 1259-67.
- 15 Whincup P, Cook D, Phillips A. et al. ABO blood groups and ischaemic heart disease in British men. Br Med J 1990; 300: 1679-82.
- 16 Koster T, Blann AD, Briet E. et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345: 152-5.
- 17 Graham I, Daly L, Refsum H. et al. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA 1997; 277: 1775-81.
- 18 Clark P, Walker I. The phenomenon known as acquired APC resistance. Br J Haematol 2001; 115: 767-73.
- 19 Most J, Schwaeble W, Drach J. et al. Regulation of the expression of ICAM-1 on human monocytes and monocytic tumor cell lines. J Immunol 1992; 148: 1635-42.
- 20 Yamada A, Hara A, Inoue M. et al. Beta 2-integrin-mediated signal up-regulates counter-receptor ICAM-1 expression on human mono-cytic cell line THP-1 through tyrosine phosphorylation. Cell Immunol 1997; 178: 9-16.
- 21 Clark P, Sattar N, Walker I, Greer I. The Glasgow Outcome, APCR and Lipid (GOAL) Pregnancy Study: significance of pregnancy associated activated protein C resistance. Thromb Haemost 2001; 85: 30-5.
- 22 Lipid Research Clinics Program In Manual of Laboratory Operations. Lipid and Lipoprotein Analysis. National Institute of Health. Beth-seda, MD: DHEW Publications; NIH 1975: 75
- 23 Bernstein I, Self S. Joint report of the myeloid section of the Second International Workshop on human leukocyte differentiation antigens. In Reinharz E, Haynes B, Nadler L, Bernstein I. eds Leucocyte Typing II: Human myeloid and haematopoietic cells. New York: Springer-Verlag; 1984: 31
- 24 Johnson J, Shaw S. In knapp W, Dorken B, Gilks W. eds Leucocyte Typing IV: White cell differentiation antigens. Oxford: Oxford University Press; 1989: 681
- 25 Maio M, Tessitori G, Pinto A. et al. Differential role of distinct determinants of intercellular adhesion molecule-1 in immunologic phenomena. J Immmunol 1989; 143: 181-8.
- 26 Heinzelman M, Polk H, Chernobelsky A. et al. Endotoxin and muramyl dipeptide modulate surface receptor expression on human mononuclear cells. Immunopharmacology 2000; 48: 117-28.
- 27 Hailer NP, Glomsda B, Blaheta RA. Astrocytic factors down-regulate the expression of major histocompatibility complex-class-II and inter-cellular adhesion molecule-1 on human mono-cytes. Neuroscience Letters 2001; 298: 33-6.
- 28 Bernatchez S, Atkinson M, Parks P. Expression of intercellular adhesion molecule-1 on macrophages in vitro as a marker of activation. Biomaterials 1997; 18: 1371-8.
- 29 Hutchinson P, Kraft N, Atkins RC. Rapid induction of intercellular adhesion molecule-1 on monocytes and myelomonocytic cell lines after interferon gamma treatment. Transplantation 1992; 54: 671-6.
- 30 Simmons D, Makgoba MW, Seed B. ICAM, an adhesion ligand of LFA-1, is homologous to the neural cell adhesion molecule NCAM. Nature 1988; 331: 624-7.
- 31 Vassallo RR, Kieber-Emmons T, Cichowski K. et al. Structure-function relationships in the activation of platelet thrombin receptors by receptor-derived peptides. J Biol Chem 1992; 267: 6081-5.
- 32 Brass LF, Pizarro S, Ahuja M. et al. Changes in the structure and function of the human thrombin receptor during receptor activation, internalization, and recycling. J Biol Chem 1994; 269: 2943-52.
- 33 Vu TKH, Hung DT, Wheaton VI. et al. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991; 64: 1057-1068.
- 34 Blann AD, Daly R, Amiral J. The influence of age, gender and ABO blood group on soluble endothelial cell markers and adhesion molecules. Br J Haematol 1996; 92: 498-500.
- 35 Clark P, Walker I, Greer I. Acquired activated protein-C resistance in pregnancy and association with increased thrombin generation and fetal weight. Lancet 1999; 353: 292-3.
- 36 Khong T, de Wolf F, Robertson W. et al. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestation-age infants. Br J Obstet Gynaecol 1986; 93: 1049-59.
- 37 Doi H, Kugiyama K, Oka H. et al. Remnant lipoproteins induce proatherothrombogenic molecules in endothelial cells through a redox-sensitive mechanism. Circulation 2000; 102: 670-6.
- 38 Ohta T, Saku K, Takata K. et al. Soluble vascular cell-adhesion molecule-1 and soluble intercellular adhesion molecule-1 correlate with lipid and apolipoprotein risk factors for coronary artery disease in children. Eur J Pediat 1999; 158: 592-8.
- 39 Niwa ST, Totsuka T. Hayashi, S. Inhibitory effect of fluvastatin, an HMG-CoA reductase inhibitor, on the expression of adhesion molecules on human monocyte cell line. Int J Immunopharmacol 1996; 18: 669-75.
- 40 Bremme K, Ostlund E, Almqvist I. et al. Enhanced thrombin generation and fibrinolytic activity in normal pregnancy and the puerperium. Obstet Gynaecol 1992; 80: 132-7.
- 41 Shi-Wen X, Panesar M, Vancheeswaran R. et al. Expression and shedding of intercellular adhesion molecule 1 and lymphocyte function-associated antigen 3 by normal and scleroderma fibroblasts. Effects of interferon-gamma, tumor necrosis factor alpha, and estrogen. Arth Rheum 1994; 37: 1689-97.
- 42 Bellamy MF, McDowell IF. Putative mechanisms for vascular damage by homocysteine. J Inherit Metab Dis 1997; 20: 307-15.
- 43 Kyrle PA, Stumpflen A, Hirschl M. et al. Levels of prothrombin fragment F1+2 is patients with hyperhomocysteinemia and a history of venous thrombosis. Thromb Haem 1997; 78: 1327-31.
- 44 Bruserud O, Akselen PE, Bergheim J. et al. Serum concentrations of E-selectin, P-selectin, ICAM-1 and interleukin 6 in acute leukaemia patients with chemotherapy-induced leucopenia and bacterial infections. Br J Haematol 1995; 91: 394-402.
- 45 Austgulen R, Lien E, Vince G. et al. Increased maternal plasma levels of soluble adhesion molecules (ICAM-1, VCAM-1, E-selectin) in pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 1997; 71: 53-8.
- 46 Krauss T, Kuhn W, Lakoma C. et al. Circulating endothelial cell adhesion molecules as diagnostic markers for the early identification of pregnant women at risk for development of preeclampsia. Am J Obstet Gynecol 1997; 177: 443-9.
- 47 Krauss T, Emons G, Kuhn W. et al. Predictive value of routine circulating soluble endothelial cell adhesion molecule measurements during pregnancy. Clin Chem 2002; 48: 1418-25.
- 48 Airoldi L, Gaffuri B, Rossi G. et al. Soluble intercellular adhesion molecule-1 serum profile in physiologic and preeclamptic pregnancy. Am J Reprod Immunol 1998; 39: 183-8.
- 49 Phocas I, Rizos D, Papoulias J. et al. A comparative study of serum soluble vascular cell adhesion molecule-1 and soluble intercellular adhesion molecule-1 in preeclampsia. J Perinatol 2000; 20: 114-9.
- 50 Djurovic S, Schjetlein R, Wisloff F. et al. Increased levels of intercellular adhesion molecules and vascular cell adhesion molecules in pre-eclampsia. Br J Obstet Gynaecol 1997; 104: 466-70.
- 51 Pigott RD, Dillon LP, Hemingway IH. et al. Soluble forms of E-selectin, ICAM-1 and VCAM-1 are present in the supernatants of cytokine activated cultured endothelial cells. Biochem Biophys Res Commun 1992; 187: 584-9.
- 52 Giavazzi R, Nicoletti MI, Chirivi RG. et al. Soluble intercellular adhesion molecule-1 (ICAM-1) is released into the serum and ascites of human ovarian carcinoma patients and in nude mice bearing tumour xenografts. Eur J Cancer 1994; 30A: 1865-70.
- 53 Colotta F, Sciacca FL, Sironi M. et al. Expression of monocyte chemotactic protein-1 by monocytes and endothelial cells exposed to thrombin. Am J Pathol 1994; 144: 975-85.
- 54 Naldini A, Carney DH, Bocci V. et al. Throm-bin enhances T cell proliferative responses and cytokine production. Cell Immunol 1993; 147: 367-77.
- 55 Languino L, Plescia J, Duperray A. Fibrinogen mediates leukocyte adhesion to vascular endothelium through an ICAM-1 dependant pathway. Cell 1993; 73: 1423-34.
- 56 Wilczynski J, Banasik M, Tchorzewski H. et al. Expression of intercellular adhesion molecule-1 on the surface of peripheral blood and decidual lymphocytes of women with pregnancy-induced hypertension. Eur J Obstet Gynecol Reprod Biol 2002; 102: 15-20.