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Bruceine B, A Potent Inhibitor of Leukocyte-Endothelial Cell Adhesion

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Abstract

Leukocyte adhesion to vascular endothelial cells is an essential step in the development of inflammatory diseases. We have searched for inhibitors of leukocyte-endothelial cell adhesion that could be used as anti-inflammatory drugs and found that bruceine B (0.2 μg/ml; 0.44 μM) inhibited human neutrophil or T cell adhesion to tumor necrosis factor-α (TNF) stimulated human umbilical vein endothelial cells (HUVEC). The inhibition of neutrophil adhesion to TNF-stimulated HUVEC by bruceine B was not derived from cytotoxic effects, as determined by measurement of the level of lactate dehydrogenase (LDH) activity in conditioned medium. The effect of bruceine B on neutrophil adhesion to HUVEC was not seen when the neutrophils were preincubated with bruceine B. However, inhibitory effects were evident when the HUVEC were preincubated with bruceine B. Bruceine B also inhibited neutrophil adhesion to lipopolysaccharide-stimulated HUVEC and T cell adhesion to TNF-stimulated HUVEC. These findings suggest that bruceine B may have anti-inflammatory activity.

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REFERENCES

  1. OSBORN, L. 1990. Leukocytes adhesion to endothelium in inflammation. Cell 62:3–6.

    Google Scholar 

  2. HARLAN, J. M. 1985. Leukocytes-endothelial interactions. Blood 65:513–525.

    Google Scholar 

  3. GAMBLE, J. R., J. M. HARLAN, S. J. KLEBANOFF, and M. A. VADAS. 1985. Stimulation of the adherence of neutrophils to umbilical vein endothelium by human recombinant tumor necrosis factor. Proc. Natl. Acad. Sci. U.S.A. 82:8667–8671.

    Google Scholar 

  4. SCHLEIMER, R. P., and B. K. RUTLEDGE. 1986. Cultured human vascular endothelial cells acquire adhesiveness for neutrophils after stimulation with interleukin 1, endotoxin, and tumor-promoting phorbol diesters. J. Immunol. 136:649–654.

    Google Scholar 

  5. CAVENDER, D. E., D. O. HASKARD, B. JOSEPH, and M. ZIFF. 1986. Interleukin 1 increases the binding of human B and T lymphocytes to endothelial cell monolayers. J. Immunol. 136:203–207.

    Google Scholar 

  6. YU, C. L., D. HASKARD, D. CAVENDER, and M. ZIFF. 1986. Effects of bacterial lipopoly-saccharide on the binding of lymphocytes to endothelial cell monolayers. J. Immunol. 136:569–573.

    Google Scholar 

  7. POHLMAN, T. H., K. A. STANNESS, P. G. BEATTY, H. D. OCHS, and J. M. HARLAN. 1986. An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-a increases neutrophil adherence by CDw 18-dependent mechanism. J. Immunol. 136:4548–1553.

    Google Scholar 

  8. BEVILAQUA, M. P., S. STENGELIN, JR. M. A. GIMBRONE, and B. SEED. 1989. Endothelial leukocytes adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243:1160–1165.

    Google Scholar 

  9. OSBORN, L., C. HESSION, R. TIZARD, C. VASSALLO, S. LUHOWSKYJ, G. CHIROSSO, and R. LOBB. 1989. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 59:1203–1211.

    Google Scholar 

  10. SIMMONS, D., M. W. WAKGOBA, and B. SEED. 1989. ICAM, an adhesion ligand for LFA-1, is homologous to neural cell adhesion molecule NCAM. Nature 331:624–627.

    Google Scholar 

  11. IIGO, Y., T. TAKAHASHI, T. TAMATANI, M. MIYASAKA, T. HIGASHIDA, H. YAGITA, K. OKUMRA, and W. TSUKADA. 1991. ICAM-1-dependent pathway is critically involved in the pathogenesis of adjuvant arthritis in rats. J. Immunol. 147:4167–4171.

    Google Scholar 

  12. KAKIMOTO, K., T. NAKAMURA, K. ISHII, T. TAKAHASHI, H. IIGO, H. YAGITA, K. OKUMURA, and K. ONOUE. 1992. The effect of anti-adhesion molecule antibody on the development of collagen-induced arthritis. Cell Immunol. 142:326–337.

    Google Scholar 

  13. KITAGAWA, I., T. MAHMUD, P. SIMANJUNTAK, K. HORI, T. UJI, and H. SHIBUYA. 1994. Indonesian medicinal plants. VIII. Chemical structures of three new triterpenoids, bruceajavanin A, dihydrobruceajavanin A, and bruceajavanin B, and a new alkaloidal glycoside, bruceacan-thinoside, from the stems of Brucea javanica (Simaroubaceae). Chem. Pharm. Bull. 42:1416–1421.

    Google Scholar 

  14. BÖYUM, A. Separation of leukocyte from blood and bone marrow. 1968. Can. J. Clin. Invest. 21:suppl. 97.

  15. JULIUS, M. M., E. SIMPSON, and L. A. HARZENBERG. 1973. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur. J. Immunol. 3:645–649.

    Google Scholar 

  16. LUSCINSKAS, F. W., A. F. BROCK, M. A. ARNAOUT, JR. and M. A. GIMBRONE. 1989. Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18)-dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium. J. Immunol. 142:2257–2263.

    Google Scholar 

  17. PAULI, B. U., and C. LEE. 1989. Organ preference of metastasis: the role of organ-specifically modulated endothelial cells. Lab. Invest. 58:379–387.

    Google Scholar 

  18. FINLAY, G. J., B. C. BAGULEY, and W. R. WILSON. 1984. A semiautomated microculture method for investigating growth inhibitory effects of cytotoxic compounds on exponentially growing carcinoma cells. Anal. Biochem. 139:272–277.

    Google Scholar 

  19. WEISSMANN, G., DUKOR, P., and ZURIER, R. B. 1971. Effect of cyclic AMP on release of lysosomal enzymes from phagocytes. Nature New Biol. 231:131–135.

    Google Scholar 

  20. OPPENHEIMER-MARKS, N., L. S. DAVIS, and P. E. LIPSKY. 1990. Human T lymphocyte adhesion to endothelial cells and transendothelial migration: alteration of receptor use relates to the activation status of both the T cell and the endothelial cell. J. Immunol. 145:140–148.

    Google Scholar 

  21. KUPCHAN, S. M., R. W. BRITTON, J. A. LACADIE, M. F. ZIEGLER, and C. W. SIGEL. 1975. The isolation and structural elucidation of bruceantin and bruceantinol, new potent antileukemic quassinoids from Brucea antidysenterica. J. Org. Chem. 40:648–654.

    Google Scholar 

  22. KIRBY, G. C., M. J. O'NEILL, J. D. PHILLIPSON, and D. C. WARHURST. 1989. In vitro studies on the mode of action of quassinoids with activity against chloroquine-resistant Plasmodium falciparum. Biochem. Pharmacol. 38:4367–4374.

    Google Scholar 

  23. PIERRE, A. R., M. GERO, C. TEMPETE, and J. POLOSKY. 1980. Structural requirements of quassinoids for the inhibition of cell transformation. Biochem. Biophys. Res. Commun. 93:675–686.

    Google Scholar 

  24. CRONSTEIN, B. N., and WEISSMANN, G. 1995. Targets for antiinflammatory drugs. Annu. Rev. Pharmacol. Toxicol. 35:449–462.

    Google Scholar 

  25. JURGENSEN, C. H., B. E. HUBER, T. P. ZIMMERMAN, and G. WOLBERG. 1990. 3-Deazaadenosine inhibits leukocyte adhesion and ICAM-1 biosynthesis in tumor necrosis factor-stimulated human endothelial cells. J. Immunol. 144:653–661.

    Google Scholar 

  26. FIRESTEIN, G. S., D. A. BULLOUGH, M. D. ERION, R. JIMENEZ, M. RAMIREZ-WEINHOUSE, J. BARANKIEWICZ, C. W. SMITH, H. E. GRUBER, and K. M. MULLANE. 1995. Inhibition of neutrophil adhesion by adenosine and an adenosine kinase inhibitor. J. Immunol. 154:326–334.

    Google Scholar 

  27. CHIANG, M. Y., H. CHAN, M. A. ZOUNES, S. M. FREIER, W. F. LIMA, and C. F. BENNET. 1991. Antisense oligonucleotides inhibit intercellular adhesion molecule 1 expression by two distinct mechanisms. J. Biol. Chem. 266:18162–18171.

    Google Scholar 

  28. BENNET, C. F., T. P. CONDON, S. GRIMM, H. CHAN, and M. Y. CHIANG. 1994. Inhibition of endothelial cell adhesion molecule expression with antisense oligonucleotides. J. Immunol. 152:3530–3540.

    Google Scholar 

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Osaka University, 1–6 Yamadaoka, Suit A, Osaka, 565, Japan

    Naoki Utoguchi, Tetsushi Nakata, Hsien Hung Cheng, Kenji Ikeda, Hiroo Makimoto, Yu Mu, Shinsaku Nakagawa, Motomasa Kobayashi, Isao Kitagawa & Tadanori Mayumi

  2. Showa College of Pharmaceutical Sciences, Tokyo, Japan

    Naoki Utoguchi

  3. Research Department of Sawai Pharmaceutical Co. Ltd., Osaka, Japan

    Tetsushi Nakata

  4. Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan

    Isao Kitagawa

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  1. Naoki Utoguchi
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  2. Tetsushi Nakata
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  3. Hsien Hung Cheng
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  4. Kenji Ikeda
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  5. Hiroo Makimoto
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Utoguchi, N., Nakata, T., Cheng, H.H. et al. Bruceine B, A Potent Inhibitor of Leukocyte-Endothelial Cell Adhesion. Inflammation 21, 223–233 (1997). https://doi.org/10.1023/A:1027374321718

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