Bruceine B, A Potent Inhibitor of Leukocyte-Endothelial Cell Adhesion |
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Authors: | Naoki Utoguchi Tetsushi Nakata Hsien Hung Cheng Kenji Ikeda Hiroo Makimoto Yu Mu Shinsaku Nakagawa Motomasa Kobayashi Isao Kitagawa Tadanori Mayumi |
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Affiliation: | (1) Faculty of Pharmaceutical Sciences, Osaka University, 1–6 Yamadaoka, Suit A, Osaka, 565, Japan;(2) Showa College of Pharmaceutical Sciences, Tokyo, Japan;(3) Research Department of Sawai Pharmaceutical Co. Ltd., Osaka, Japan;(4) Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan |
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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 g/ml; 0.44 M) inhibited human neutrophil or T cell adhesion to tumor necrosis factor- (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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