A novel role for the bactericidal/permeability increasing protein in interactions of gram-negative bacterial outer membrane blebs with dendritic cells.
The bactericidal/permeability-increasing protein (BPI) is thought to play an important role in killing and clearance of Gram-negative bacteria and the neutralization of endotoxin. A possible role for BPI in clearance of cell-free endotoxin has also been suggested based on studies with purified endotoxin aggregates and blood monocytes. Because the interaction of BPI with cell-free endotoxin, during infection, occurs mainly in tissue and most likely in the form of shed bacterial outer membrane vesicles ("blebs"), we examined the effect of BPI on interactions of metabolically labeled ([(14)C]-acetate) blebs purified from Neisseria meningitidis serogroup B with either human monocyte-derived macrophages or monocyte-derived dendritic cells (MDDC). BPI produced a dose-dependent increase (up to 3-fold) in delivery of (14)C-labeled blebs to MDDC, but not to monocyte-derived macrophages in the presence or absence of serum. Both, fluorescently labeled blebs and BPI were internalized by MDDC under these conditions. The closely related LPS-binding protein, in contrast to BPI, did not increase association of the blebs with MDDC. BPI-enhanced delivery of the blebs to MDDC did not increase cell activation but permitted CD14-dependent signaling by the blebs as measured by changes in MDDC morphology, surface expression of CD80, CD83, CD86, and MHC class II and secretion of IL-8, RANTES, and IP-10. These findings suggest a novel role of BPI in the interaction of bacterial outer membrane vesicles with dendritic cells that may help link innate immune recognition of endotoxin to Ag delivery and presentation.
Inflammation Program, University of Iowa and Iowa City Veterans Affairs Medical Center, IA, USA.
Hendrik
H
Schultz
Janet
J
Hume
De Sheng
DS
Zhang
Theresa L
TL
Gioannini
Jerrold P
JP
Weiss
D000209:Acute-Phase Proteins / Q000276:immunology / Q000378:metabolism; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000276:immunology* / Q000378:metabolism; D001693:Biological Transport, Active / Q000276:immunology; D001798:Blood Proteins / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004731:Endotoxins / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D000942:Antigens, Bacterial; D015703:Antigens, CD; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D018925:Chemokines; D004731:Endotoxins; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D000099231:Lipopolysaccharide-Binding Protein; C021623:bactericidal permeability increasing protein