Abstract
Antimicrobial effector proteins are a key mechanism for the innate immune system to combat pathogens once they infect the host. We report the identification and cloning of the mouse homologue of human bactericidal permeability/increasing protein (BPI). Mouse BPI is constitutively expressed in lymphatic organs and tissues as well as in mouse testis. Upon stimulation with different TLR ligands, mouse BPI is strongly expressed in granulocytes and, surprisingly, in bone marrow-derived dendritic cells. Mouse BPI is most strongly induced by bacterial LPS through a signaling pathway that is completely dependent on TLR4-Toll/IL-1R domain-containing adaptor inducing IFN-beta. Functional studies revealed that mouse BPI does have the potential to neutralize LPS and inhibits bacterial growth. Mouse BPI is expressed in granulocytes and bone marrow-derived dendritic cells, and the transcriptional activation is controlled by TLRs.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adaptor Proteins, Signal Transducing / immunology
-
Adaptor Proteins, Vesicular Transport / immunology
-
Amino Acid Sequence
-
Animals
-
Antimicrobial Cationic Peptides
-
Blood Proteins / genetics*
-
Blood Proteins / immunology*
-
Blood Proteins / metabolism
-
Blotting, Northern
-
Bone Marrow Cells / immunology
-
Cloning, Molecular
-
Dendritic Cells / immunology
-
Endotoxins / metabolism*
-
Granulocytes / immunology
-
Granulocytes / metabolism
-
Humans
-
Interferon-beta / immunology
-
Interferon-beta / metabolism*
-
Lipopolysaccharides / immunology
-
Macrophages / immunology
-
Macrophages / microbiology
-
Membrane Proteins / genetics*
-
Membrane Proteins / immunology*
-
Membrane Proteins / metabolism
-
Mice
-
Molecular Sequence Data
-
Myeloid Differentiation Factor 88
-
RNA, Messenger / analysis
-
Receptors, Interleukin-1 / immunology
-
Receptors, Interleukin-1 / metabolism*
-
Reverse Transcriptase Polymerase Chain Reaction
-
Salmonella Infections / immunology
-
Salmonella typhimurium / immunology
-
Sequence Homology, Amino Acid
-
Toll-Like Receptors / immunology
-
Toll-Like Receptors / metabolism*
-
Transcription, Genetic / immunology
Substances
-
Adaptor Proteins, Signal Transducing
-
Adaptor Proteins, Vesicular Transport
-
Antimicrobial Cationic Peptides
-
Blood Proteins
-
Endotoxins
-
Lipopolysaccharides
-
MYD88 protein, human
-
Membrane Proteins
-
Myd88 protein, mouse
-
Myeloid Differentiation Factor 88
-
RNA, Messenger
-
Receptors, Interleukin-1
-
TICAM-1 protein, mouse
-
Toll-Like Receptors
-
bactericidal permeability increasing protein
-
Interferon-beta