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DOI: 10.1055/s-0037-1613407
Distinct accumulation patterns of soluble forms of E-selectin, VCAM-1 and ICAM-1 upon infusion of TNFα in tumor patients
Financial support: The financial support of the Universiteits Stimulerings Fonds of the Vrije Universiteit is gratefully acknowledged.Publikationsverlauf
Received
22. April 2002
Accepted after resubmission
28. Februar 2003
Publikationsdatum:
08. Dezember 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/200306/lookinside/thumbnails/10-1055-s-0037-1613407-1.jpg)
Summary
The transmigration of leukocytes across the endothelium is a prerequisite for the inflammatory process. Leukocyte-endothelium interaction is regulated by several endothelial adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. Their expression is enhanced by inflammatory mediators, such as TNFα. In vivo a small part of these adhesion molecules is shed by proteases, and can be detected in the circulation. In this study, the time course of the TNFα-induced accumulation in the blood of three circulating soluble adhesion molecules, sE-selectin, sICAM-1 and sVCAM-1, was studied in plasma samples of tumor patients enrolled in a phase I trial receiving TNFα. Two different cohorts were studied. Eleven patients received a continuous 24-hour TNFα infusion while 10 other patients received a 5-day continuous TNFα infusion. After 24 hours of TNFα infusion sE-selectin levels increased by 1985 ± 312 %, sVCAM-1 by 301± 19 % and sICAM-1 by 445 ± 82 %. Differences in accumulation patterns were observed after 5 days of continuous TNFα infusion. sVCAM-1 and sICAM-1 levels showed an increase during the infusion with a maximum at 3 to 5 days and stayed elevated after discontinuation of the TNFα infusion. In contrast, sE-selectin reached its peak at day 1 and declined thereafter. In conclusion, sVCAM-1 and sICAM-1 show a different accumulation pattern upon TNFα infusion as compared to sE-selectin in man.
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References
- 1 Bevilacqua MP, Nelson RM, Mannori G, Cecconi O. Endothelial-leukocyte adhesion molecules in human disease. Annu Rev Med 1994; 45: 361-78.
- 2 Gearing AJ, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993; 14: 506-12.
- 3 Leca G, Mansur SE, Bensussan A. Expression of VCAM-1 (CD106) by a subset of TCR gamma delta-bearing lymphocyte clones. Involvement of a metalloprotease in the specific hydrolytic release of the soluble isoform. J Immunol 1995; 154: 1069-77.
- 4 Hummel V, Kallmann BA, Wagner S. et al. Production of MMPs in human cerebral endothelial cells and their role in shedding adhesion molecules. J Neuropathol Exp Neurol 2001; 60: 320-7.
- 5 Becker JC, Termeer C, Schmidt RE, Brocker EB. Soluble intercellular adhesion molecule-1 inhibits MHC-restricted specific T cell/tumor interaction. J Immunol 1993; 151: 7224-32.
- 6 Croucher PI, Wang F, Hargreaves PG. Interleukin-6 receptor shedding. a possible role for members of the ADAM family. Biochem Soc Trans 1999; 27: 224-8.
- 7 Koolwijk P, Sidenius N, Peters E. et al. Proteolysis of the urokinase-type plasminogen activator receptor by metalloproteinase-12. implication for angiogenesis in fibrin matrices. Blood 2001; 97: 3123-31.
- 8 Tamasawa N, Murakami H, Matsui J. et al. An oxidized derivative of cholesterol increases the release of soluble vascular cell adhesion molecule-1 from human umbilical vein endothelial cells in culture. Biochim Biophys Acta 2001; 1531: 178-87.
- 9 Bauvois B. Transmembrane proteases in focus. diversity and redundancy?. J Leukoc Biol 2001; 70: 11-7.
- 10 Hooper NM, Karran EH, Turner AJ. Membrane protein secretases. Biochem J 1997; 321: 265-79.
- 11 Bonomini M, Reale M, Santarelli P, Stuard S, Settefrati N, Albertazzi A. Serum levels of soluble adhesion molecules in chronic renal failure and dialysis patients. Nephron 1998; 79: 399-407.
- 12 Pigott R, Dillon LP, Hemingway IH, Gearing AJ. 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.
- 13 Rieckmann P, Michel U, Albrecht M, Bruck W, Wockel L, Felgenhauer K. Soluble forms of intercellular adhesion molecule-1 (ICAM-1) block lymphocyte attachment to cerebral endothelial cells. J Neuroimmunol 1995; 60: 9-15.
- 14 Romano M, Sironi M, Toniatti C. et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 1997; 6: 315-25.
- 15 Jager A, van Hinsbergh VW, Kostense PJ. et al. Increased levels of soluble vascular cell adhesion molecule 1 are associated with risk of cardiovascular mortality in type 2 diabetes. the Hoorn study. Diabetes 2000; 49: 485-91.
- 16 Parissis JT, Venetsanou KF, Mentzikof DG. et al. Plasma levels of soluble cellular adhesion molecules in patients with arterial hypertension. Correlations with plasma endothelin-1. 2001; 12: 350-6.
- 17 Peter K, Nawroth P, Conradt C. et al. Circulating vascular cell adhesion molecule-1 correlates with the extent of human atherosclerosis in contrast to circulating intercellular adhesion molecule-1, E-selectin, P-selectin, and thrombomodulin. Arterioscler Thromb Vasc Biol 1997; 17: 505-12.
- 18 De Caterina R, Bourcier T, Laufs U. et al. Induction of endothelial-leukocyte interaction by interferon-gamma requires coactivation of nuclear factor-kappaB. Arterioscler Thromb Vasc Biol 2001; 21: 227-32.
- 19 Smulders RA, Stehouwer CD, Schalkwijk CG, Donker AJ, van Hinsbergh VW, Te Koppele JM. Distinct associations of HbA1c and the urinary excretion of pentosidine, an advanced glycosylation end-product, with markers of endothelial function in insulin-dependent diabetes mellitus. Thromb Haemost 1998; 80: 52-7.
- 20 De Mattia G, Bravi MC, Costanzo A. et al. Effects of insulin on in vitro vascular cell adhesion molecule-1 expression and in vivo soluble VCAM-1 release. Diabetologia 1999; 42: 1235-9.
- 21 Marfella R, Esposito K, Giunta R. et al. Circulating adhesion molecules in humans. role of hyperglycemia and hyperinsulinemia. Circulation 2000; 101: 2247-51.
- 22 Jilma B, Blann A, Pernerstorfer T. et al. Regulation of adhesion molecules during human endotoxemia. No acute effects of aspirin. Am J Respir Crit Care Med 1999; 159: 857-63.
- 23 Pober JS, Bevilacqua MP, Mendrick DL, Lapierre LA, Fiers W, Gimbrone Jr MA. Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol 1986; 136: 1680-7.
- 24 Fassbender K, Mossner R, Motsch L, Kischka U, Grau A, Hennerici M. Circulating selectin-and immunoglobulin-type adhesion molecules in acute ischemic stroke. Stroke 1995; 26: 1361-4.
- 25 Bauer KA, ten Cate H, Barzegar S, Spriggs DR, Sherman ML, Rosenberg RD. Tumor necrosis factor infusions have a procoagulant effect on the hemostatic mechanism of humans. Blood 1989; 74: 165-72.
- 26 Sherman ML, Spriggs DR, Arthur KA, Imamura K, Frei III E, Kufe DW. Recombinant human tumor necrosis factor administered as a five-day continuous infusion in cancer patients. phase I toxicity and effects on lipid metabolism. J Clin Oncol 1988; 6: 344-50.
- 27 Becker A, van Hinsbergh VW, Kostense PJ. et al. Serum homocysteine is weakly associated with von Willebrand factor and soluble vascular cell adhesion molecule 1, but not with C-reactive protein in type 2 diabetic and non-diabetic subjects - The Hoorn Study. Eur J Clin Invest 2000; 30: 763-70.
- 28 Becker A, van Hinsbergh VW, Jager A. et al. Why is soluble intercellular adhesion molecule-1 related to cardiovascular mortality?. Eur J Clin Invest. 2002; 32: 1-8.
- 29 Sidenius N, Sier CF, Blasi F. Shedding and cleavage of the urokinase receptor (uPAR). identification and characterisation of uPAR fragments in vitro and in vivo. FEBS Lett 2000; 475: 52-6.
- 30 Nelimarkka LO, Nikkari ST, Ravanti LS, Kahari VM, Jarvelainen HT. Collagenase-1, stromelysin-1 and 92 kDa gelatinase are associated with tumor necrosis factor-alpha induced morphological change of human endothelial cells in vitro. Matrix Biol 1998; 17: 293-304.
- 31 Thomson AW, Satoh S, Nussler AK. et al. Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes. Clin Exp Immunol 1994; 95: 83-90.