Presentation: The Anca Target Antigen Bactericidal/Permeability-Increasing Protein (BPI) Co-Localizes with Gram-Negative Bacterial Outer Membrane Blebs in Lamp-1+ Compartments of Dendritic Cells (2007)

2010 The Anca Target Antigen Bactericidal/Permeability-Increasing Protein (BPI) Co-Localizes with Gram-Negative Bacterial Outer Membrane Blebs in Lamp-1+ Compartments of Dendritic Cells

PURPOSE: Previous data in animal models and infected vasculitis patients indicated a link between bacterial components and the generation of ANCA, however, the mechanisms remained as yet unknown. The bactericidal/permeability-increasing protein (BPI) plays an important role in killing and clearance of Gram-negative bacteria (GNB) and neutralization of endotoxin. BPI is also a target antigen of ANCA in conditions where an exposure of host tissue to GNB and/or their endotoxin has become diffuse and chronic as e.g. in cystic fibrosis. A possible role for BPI in clearance of cell-free endotoxin has been suggested, based on studies with purified endotoxin aggregates and blood monocytes.
METHODS: Since 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 (OMV or “blebs”), we examined the effect of BPI on interactions of ([14C]-acetate) metabolically labeled OM blebs purified from Neisseria meningitidis serogroup B with either human monocyte-derived macrophages (MDM) or dendritic cells (MDDC).
RESULTS: BPI produced a dose-dependent increase in delivery of [14C]-labeled blebs to MDDC, but not to MDM in the presence or absence of serum. Moreover, both fluorescently labeled blebs and BPI were internalized by MDDC when these cells were incubated with blebs + BPI and co-localized in LAMP-1-positive compartments. The closely related lipopoysaccharide-binding protein, LBP, 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 LBP/CD14-dependent signaling and MDDC activation.
CONCLUSIONS: These findings suggest a novel role of the ANCA target antigen BPI in the interaction of bacterial outer membrane vesicles with dendritic cells that may link innate immune recognition of cell-free endotoxin to bacterial and host antigen delivery and presentation by professional antigen presenting cells.

 H. Schultz, None; Y. Nakano, None; J.R. Hume, None; D. Zhang, None; T.L. Gioannini, None; J.P. Weiss, None.