Receptor for advanced glycation end products facilitates host defense during Escherichia coli-induced abdominal sepsis in mice.
BACKGROUND
The receptor for advanced glycation end products (RAGE) mediates a variety of inflammatory responses.


METHODS
To determine the role of RAGE in the innate immune response to abdominal sepsis caused by Escherichia coli, RAGE-deficient (RAGE(-/-)) and normal wild-type mice were intraperitoneally injected with E. coli. In a separate experiment, wild-type mice received either anti-RAGE immunoglobulin (Ig) G or control IgG.


RESULTS
E. coli sepsis resulted in an up-regulation of RAGE in the liver but not in the lungs. RAGE-deficient mice demonstrated an enhanced bacterial outgrowth in their peritoneal cavity and increased dissemination of the infection, accompanied by increased hepatocellular injury and exaggerated systemic cytokine release and coagulation activation, 20 h after intraperitoneal administration of E. coli. Wild-type mice treated with anti-RAGE IgG also displayed a diminished defense against the growth and/or dissemination of E. coli. RAGE was important for the initiation of the host response, as reflected by a reduced immune and procoagulant response early after intraperitoneal injection of E. coli lipopolysaccharide.


CONCLUSIONS
These data are the first to suggest that intact RAGE signaling contributes to an effective antibacterial defense during E. coli sepsis, thereby limiting the accompanying inflammatory and procoagulant response.
van Zoelen
Marieke A D
MA
Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. M.A.vanZoelen@amc.uva.nl
Schmidt
Ann-Marie
AM
Florquin
Sandrine
S
Meijers
Joost C
JC
de Beer
Regina
R
de Vos
Alex F
AF
Nawroth
Peter P
PP
Bierhaus
Angelika
A
van der Poll
Tom
T
D000818:Animals; D001777:Blood Coagulation; D015169:Colony Count, Microbial; D016207:Cytokines / Q000097:blood; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D005260:Female; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010529:Peritoneal Cavity / Q000382:microbiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology
D016207:Cytokines; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic