Murine bactericidal/permeability-increasing protein inhibits the endotoxic activity of lipopolysaccharide and gram-negative bacteria.
Recognition of LPS by TLR4 initiates inflammatory responses inducing potent antimicrobial immunity. However, uncontrolled inflammatory responses can be detrimental. To prevent the development of septic shock during an infection with Gram-negative bacteria, the immune system has developed mechanisms to neutralize LPS by specialized proteins. In this study, we report the recombinant expression and functional characterization of the mouse homolog of human bactericidal/permeability-increasing protein (BPI). Purified recombinant mouse BPI was able to neutralize LPS-mediated activation of macrophages and to block LPS-dependent maturation of dendritic cells. Recombinant mouse BPI neutralized the capacity of Gram-negative bacteria to activate immune cells, but did not influence the stimulatory properties of Gram-positive bacteria. Unlike human BPI, mouse BPI failed to kill or inhibit the growth of Pseudomonas aeruginosa. Together, these data demonstrate that murine BPI is a potent LPS-neutralizing protein that may limit innate immune responses during Gram-negative infections.
Wittmann
Irene
I
Microbiological Institute-Clinical Microbiology, Immunology and Hygiene, University of Erlangen-Nuremberg, Erlangen, Germany.
Schönefeld
Marc
M
Aichele
Diana
D
Groer
Gerhard
G
Gessner
André
A
Schnare
Markus
M
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000276:immunology / Q000378:metabolism; D001798:Blood Proteins / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D004926:Escherichia coli / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D006090:Gram-Negative Bacteria / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D008262:Macrophage Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011506:Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000254:growth & development; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008070:Lipopolysaccharides; D011506:Proteins; D011994:Recombinant Proteins; C021623:bactericidal permeability increasing protein