Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response.
While the initiation of the adaptive and innate immune response is well understood, less is known about cellular mechanisms propagating inflammation. The receptor for advanced glycation end products (RAGE), a transmembrane receptor of the immunoglobulin superfamily, leads to perpetuated cell activation. Using novel animal models with defective or tissue-specific RAGE expression, we show that in these animal models RAGE does not play a role in the adaptive immune response. However, deletion of RAGE provides protection from the lethal effects of septic shock caused by cecal ligation and puncture. Such protection is reversed by reconstitution of RAGE in endothelial and hematopoietic cells. These results indicate that the innate immune response is controlled by pattern-recognition receptors not only at the initiating steps but also at the phase of perpetuation.
Liliensiek
Birgit
B
Department of Molecular Immunology, Division of Tumor Immunology, German Cancer Research Center, Heidelberg, Germany.
Weigand
Markus A
MA
Bierhaus
Angelika
A
Nicklas
Werner
W
Kasper
Michael
M
Hofer
Stefan
S
Plachky
Jens
J
Gröne
Herman-Josef
HJ
Kurschus
Florian C
FC
Schmidt
Ann Marie
AM
Yan
Shi Du
SD
Martin
Eike
E
Schleicher
Erwin
E
Stern
David M
DM
Hämmerling G
G ünterJ
Gü
Nawroth
Peter P
PP
Arnold
Bernd
B
D000818:Animals; D002432:Cecum / Q000293:injuries; D007107:Immune System / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010538:Peritonitis / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism; D013997:Time Factors
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic