Bruceine B, a potent inhibitor of leukocyte-endothelial cell adhesion.
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.
Utoguchi
N
N
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Nakata
T
T
Cheng
H H
HH
Ikeda
K
K
Makimoto
H
H
Mu
Y
Y
Nakagawa
S
S
Kobayashi
M
M
Kitagawa
I
I
Mayumi
T
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005900:Glaucarubin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects; D036702:Quassins; D013601:T-Lymphocytes / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D036702:Quassins; C024965:bruceine B; D005900:Glaucarubin