Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein.
Endothelial cells stimulated by LPS express E-selectin, which plays an important role in mediating neutrophil adhesion during inflammation. E-selectin is induced within 1-2 h, peaks at 4-6 h, and gradually returns to basal level by 24 h. rBPI21, a recombinant N-terminal fragment of human bactericidal/permeability-increasing protein (BPI), inhibited LPS-induced E-selectin expression when added at the same time as, and up to 6 h after, LPS. Delayed administration of rBPI21 also affected LPS-mediated activation of the nuclear factor, NF-kappa B. Two to 4 h following LPS addition to endothelial cells, when NF-kappa B was already activated, addition of rBPI21 resulted in marked reduction of NF-kappa B detectable at 4 or 6 h. These results indicate that endothelial activation requires continuous presence of LPS, and rBPI21 acts to reverse LPS-mediated endothelial activation by interrupting the on-going LPS signal.
Huang
K
K
Department of Immunology, XOMA Corporation, Berkeley, California 94710, USA.
Fishwild
D M
DM
Wu
H M
HM
Dedrick
R L
RL
D023181:Antimicrobial Cationic Peptides; D001483:Base Sequence; D001798:Blood Proteins / Q000494:pharmacology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014470:Umbilical Cord
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins; C021623:bactericidal permeability increasing protein