A recombinant amino-terminal fragment of bactericidal/permeability increasing protein (rBPI23) inhibits soluble CD14-mediated lipopolysaccharide-induced endothelial adherence for human neutrophils.
Exposure of cultured human umbilical vein endothelial cells (HUVEC) to lipopolysaccharide (LPS) or interleukin 1 (IL-1) causes increased expression of adhesion molecules such as E-selectin and CD54 by HUVEC and consequently increased adherence of peripheral blood neutrophils. A recombinant aminoterminal fragment of bactericidal/permeability increasing protein (rBPI23) was shown to specifically block the LPS-induced adhesiveness of HUVEC for neutrophils. rBPI23 also prevented the LPS- but not IL-1 beta-induced upregulation on HUVEC of E-selectin and CD54. Furthermore, this inhibition was evident even when the endothelial cells were exposed to LPS for up to 1-2 h prior to rBPI23 addition. The inhibitory effects of an anti-CD14 monoclonal antibodies (mAb) were similar to those of rBPI23. Combination of the anti-CD14 mAb and rBPI23 resulted inhibition greater than either one used alone. These studies demonstrate that rBPI23 acts as a specific and potent inhibitor of soluble CD14-mediated LPS induction.
Huang
K
K
Department of Immunology, XOMA Corporation, Berkeley, California 94710, USA.
Conlon
P J
PJ
Fishwild
D M
DM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000502:physiology*; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D009504:Neutrophils / Q000166:cytology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D014471:Umbilical Veins; D015854:Up-Regulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011994:Recombinant Proteins; C021623:bactericidal permeability increasing protein; D018799:Intercellular Adhesion Molecule-1