title: An opsonic function of the neutrophil bactericidal/permeability-increasing protein depends on both its N- and C-terminal domains.
abstract: The host response to Gram-negative bacterial infection is influenced by two homologous lipopolysaccharide (LPS)-interactive proteins, LPS-binding protein (LBP) and the bacteridical/permeability-increasing protein (BPI). Both proteins bind LPS via their N-terminal domains but produce profoundly different effects: BPI and a bioactive N-terminal fragment BPI-21 exert a selective and potent antibacterial effect upon Gram-negative bacteria and suppress LPS bioactivity whereas LBP is not toxic toward Gram-negative bacteria and potentiates LPS bioactivity. The latter effect of LBP requires the C-terminal domain for delivery of LPS to CD14, so we postulated that the C-terminal region of BPI may serve a similar delivery function but to distinct targets. LBP, holoBPI, BPI-21, and LBP/BPI chimeras were compared for their ability to promote uptake by human phagocytes of an encapsulated, phagocytosis-resistant strain of Escherichia coli. We show that only bacteria preincubated with holoBPI are ingested by neutrophils and monocytes. These findings suggest that, when extracellular holoBPI is bound via its N-terminal domain to Gram-negative bacteria, the C-terminal domain promotes bacterial attachment to neutrophils and monocytes, leading to phagocytosis. Therefore, analogous to the role of the C-terminal domain of LBP in delivery of LPS to CD14, the C-terminal domain of BPI may fulfill a similar function in BPI-specific disposal pathways for Gram-negative bacteria.
authors.affiliation: Department of Microbiology, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Iovine
authors.forename: P
authors.initials: P
authors.lastname: Elsbach
authors.forename: J
authors.initials: J
authors.lastname: Weiss
mesh_terms: D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins; D008854:Microscopy, Electron; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D009895:Opsonin Proteins / Q000378:metabolism*; D010587:Phagocytosis
chemical_list: D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008565:Membrane Proteins; D009895:Opsonin Proteins; C021623:bactericidal permeability increasing protein