Echinomycin Suppresses the Pyrogenic Effects of Endotoxin and Interleukin- lβ in Human Endothelial Cells and Peripheral Blood Mononuclear Cells

Summary

Endotoxin (LPS) and interleukin-1(3 (IL-iβ) increased in a dose-dependent manner the expression of tissue factor, an ubiquitous membrane-anchored glycoprotein that initiates blood coagulation at the surface of human umbilical vein endothelial cells (HUVEC) and human peripheral blood mononuclear cells (PBMC). Echinomycin, a cyclic octapeptide of microbial origin strongly inhibited LPS- and IL-1β-induced tissue factor expression in HUVEC and PBMC with IC₅₀ values in the subnanomolar range at the same time it reduced LPS and IL-iβ-induced expression of intercellular adhesion molecule-1 (ICAM-1, CD54) on HUVEC (IC₅₀ = 0.4 ± 0.1 and 0.3 ± 0.2 nM respectively). Echinomycin also reduced LPS-induced secretion of IL-iβ and IL-6 by human PBMC (IC₅₀ = 10 ± 2 and 3 ± 0.5 nM respectively). These observations demonstrate that echinomycin protects endothelial cells and PBMC from the pyrogenic effect of LPS and 1β.

• References

• 1 Nemerson Y. Tissue Factor and Haemostasis. Blood 1988; 71: 1-8
• 2 Bevilacqua MP, Pober JS, Majeau GR, Cotran RS, Gimbrone MA. Interleukin 1 induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med 1984; 160: 618-623
• 3 Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone MA. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: Characterisation and comparison with the actions of interleukin 1. Proc Natl Acad Sci USA 1986; 83: 4533-4537
• 4 Colucci M, Balconi G, Lorenzet R, Pietra A, Locati D, Donati MB, Semeraro N. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 1983; 71: 1893-1896
• 5 Corbaz R, Ettlinger L, Gaumann E, Kradolfer F, Neipp L, Reusser P, Zahner H. Stoffwechselprodukte von Actinomyceten. Echinomycin. Helv Chim Acta 1957; 40: 199-204
• 6 Bhatia MC, Thyagarojan TR, Srivastova OP, Anand N, Vora VC, Indian I. Quinoxaline antibiotics from a streptomyces species (X-53). Chem 1963; 1: 277-278
• 7 Yoshidag T, Katagiri K, Yokozawa S. Studies on quinoxaline antibiotics II. Isolation and properties of quinomycins A, B and C. J Antibiot 1961; 14: 330-334
• 8 Tsunodo A. Chemoprophylaxis of poliomyelitis in mice with quinomycin. J Antibiot 1962; 15: 60-66
• 9 Sato K, Yoshida T, Katagiri K. Inhibition of RNA synthesis in E. Coli protoplasts by quinomycins A and C J Antibiot 1967; 20: 188-189
• 10 Katagiri K, Sugiura K. Antitumor action of the quinoxaline antibiotics. Antimicrob Agents Chemother 1961; 61: 162-168
• 11 Matsura S. Studies on quinoxaline antibiotics IV. Selective antitumor activity of each quinoxaline antibiotic. J Antibiot 1965; 18: 43-46
• 12 Jaffe E, Nachmann RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 1973; 52: 2745-2756
• 13 Boyum A. Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol 1976; 5: 9-15
• 14 Surprenant YM, Zuckerman SH. A novel microtiter plate assay for the quantitation of procoagulant activity on adherent monocytes, macrophage and endothelial cells. Thromb Res 1989; 53: 339-342
• 15 Herbert JM, Savi P, Laplace MC, Lale A, Dol F, Dumas A, Labit C, Minty A. IL-4 and IL-13 exhibit comparable abilities to reduce pyrogen-induced expression of procoagulant activity in endothelial cells and monocytes. FEBS Lett 1993; 328: 268-270
• 16 Gimbrone MA. In: Vascular endothelium in hemostasis and thrombosis. Gimbrone MA. ed Curchill Livingstone; New York: 1989: 1-43
• 17 Nawroth PP, Handley DA, Esmon CT, Stem DM. Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity. Proc Natl Acad Sci USA 1986; 83: 3460-3464
• 18 Moore KL, Andreoli SP, Esmon NL, Esmon CT, Bang NU. Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. J Clin Invest 1987; 79: 124-130
• 19 Colucci M, Balconi G, Lorenzet R, Pietra A, Locati D, Donati MB, Semararo N. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 1983; 71: 1893-1896
• 20 Herbert JM, Savi P, Laplace MC, Dumas A, Dol F. Chelerthrine, a selective protein kinase C inhibitor, counteracts pyrogen-induced expression of tissue factor without effect on thrombomodulin down-regulation in endothelial cells. Thromb Res 1993; 71: 487-493
• 21 Carson SD, Ross SE, Bach R, Guha A. An inhibitory monoclonal antibody against human tissue factor. Blood 1987; 70: 490-493
• 22 Waring MJ, Wakelin LP. Echinomycin: a bifunctional intercalating antibiotic. Nature 1974; 252: 653-657
• 23 Rampart M, Williams TJ. Evidence that neutrophil accumulation induced by interleukin-1 requires both local protein biosynthesis and neutrophil CD18 antigen expression in vivo. Br J Pharmacol 1988; 94: 1143-1149
• 24 Arfors KE, Lundberg C, Lindbom L, Lundberg K, Beatty PG, Harlan JM. A monoclonal antibody to the membrane glycoprotein complex CD 18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood 1987; 69: 338-340
• 25 McIntyre KW, Stepan GJ, Kolinsky KD, Benjamin WR, Kaffka KL, Campen CA, Chizzonite RA, Kilian PL. Inhibition of interleukin 1 (IL-1) binding and bioactivity in vitro and modulation of acute inflammation in vivo by IL-1 receptor antagonist and anti-IL-1 receptor monoclonal antibody. J Exp Med 1991; 173: 931-939
• 26 Dustin ML, Rothlein R, Bahn AK, Dinarello CA, Springer TA. Induction by IL-1 and interferon-y: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 1986; 137: 245-254
• 27 Lane TA, Lamkin GE, Wancewicz EV. Protein kinase C inhibitors block the enhanced expression of intercellular adhesion molecule-1 on endothelial cells activated by interleukin-1, lipopolysaccharide and tumor necrosis factor. Biochem Biophys Res Commun 1990; 172: 1273-1281
• 28 Aderka D, Fisher S, Levo Y, Holtmann H, Hahn T, Wallach D. Cachectin/tumour-necrosis-factor production by cancer patients. Lancet 1985; 2: 1190-1191
• 29 Foster BJ, Clagett-Carr K, Shoemaker DD, Suffness M, Plowman J, Trissel LA, Grieshaber CK, Leyland-Jones B. Echinomycin: the first bifunctional intercalating agent in clinial trials. Invest New Drugs 1986; 3: 403-410