Bactericidal/permeability-increasing protein promotes complement activation for neutrophil-mediated phagocytosis on bacterial surface.
The neutrophil bactericidal/permeability-increasing protein (BPI) has both bactericidal and lipopolysaccharide-neutralizing activities. The present study suggests that BPI also plays an important role in phagocytosis of Escherichia coli by neutrophils through promotion of complement activation on the bacterial surface. Flow cytometric analysis indicated that fluorescein-labelled E. coli treated with BPI were phagocytosed in the presence of serum at two- to five-fold higher levels than phagocytosis of the bacteria without the treatment. In contrast, phagocytosis of the fluoresceined bacteria with or without treatment by BPI did not occur at all in the absence of serum. The phagocytosis stimulated by BPI and serum was dose-dependent. The effect of BPI on phagocytosis in the presence of serum was not observed on Gram-positive bacteria (Staphylococcus aureus). Interestingly, the complement C3b/iC3b fragments were deposited onto the bacterial surface also as a function of the BPI concentration under conditions similar to those for phagocytosis. Furthermore, the BPI-promoted phagocytosis was blocked completely by anti-C3 F(ab')(2) and partially by anti-complement receptor (CR) type 1 and/or anti-CR type 3. These findings suggest that BPI accelerates complement activation to opsonize bacteria with complement-derived fragments, leading to stimulation of phagocytosis by neutrophils via CR(s).
Nishimura
H
H
Department of Hygienic Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan. bowmore@agbi.tsukuba.ac.jp
Gogami
A
A
Miyagawa
Y
Y
Nanbo
A
A
Murakami
Y
Y
Baba
T
T
Nagasawa
S
S
D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity; D001798:Blood Proteins / Q000276:immunology*; D002460:Cell Line; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology; D003179:Complement C3b / Q000276:immunology; D003470:Culture Media; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000276:immunology; D006801:Humans; D016177:Macrophage-1 Antigen / Q000276:immunology; D008565:Membrane Proteins; D009504:Neutrophils / Q000276:immunology*; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D017463:Receptors, Complement 3b / Q000276:immunology
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D003176:Complement C3; D003470:Culture Media; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; D009895:Opsonin Proteins; D017463:Receptors, Complement 3b; C021623:bactericidal permeability increasing protein; D003179:Complement C3b