Bruceine B, a potent inhibitor of leukocyte-endothelial cell adhesion.

N Utoguchi, T Nakata, H H Cheng, K Ikeda, H Makimoto, Y Mu, S Nakagawa, M Kobayashi, I Kitagawa, T Mayumi

Faculty of Pharmaceutical Sciences, Osaka University, Japan.

Inflammation 1997 Apr

filter terms:

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 microgram/ml; 0.44 microM) inhibited human neutrophil or T cell adhesion to tumor necrosis factor-alpha (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.

Citation

N Utoguchi, T Nakata, H H Cheng, K Ikeda, H Makimoto, Y Mu, S Nakagawa, M Kobayashi, I Kitagawa, T Mayumi. Bruceine B, a potent inhibitor of leukocyte-endothelial cell adhesion. Inflammation. 1997 Apr;21(2):223-33