Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response
Birgit Liliensiek, … , Peter P. Nawroth, Bernd Arnold
Birgit Liliensiek, … , Peter P. Nawroth, Bernd Arnold
Published June 1, 2004
Citation Information: J Clin Invest. 2004;113(11):1641-1650. https://doi.org/10.1172/JCI18704.
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Article Immunology

Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response

Abstract

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.

Authors

Birgit Liliensiek, Markus A. Weigand, Angelika Bierhaus, Werner Nicklas, Michael Kasper, Stefan Hofer, Jens Plachky, Herman-Josef Gröne, Florian C. Kurschus, Ann Marie Schmidt, Shi Du Yan, Eike Martin, Erwin Schleicher, David M. Stern, Günter J. Hämmerling, Peter P. Nawroth, Bernd Arnold

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RAGE–/– and Tie2RAGE mice develop a normal immune response in EAE. Age- ...
RAGE–/– and Tie2RAGE mice develop a normal immune response in EAE. Age- and sex-matched mice were sensitized against oligodendrocyte glycoprotein (MOG35–55) and were monitored for the onset of clinical signs on a daily basis (see Methods). (A) EAE response in WT and RAGE–/– mice. WT indicates C57BL/6 ∞ 129/Sv mice. The mean clinical score represents a summary of two independent experiments each for WT and for RAGE–/–. WT, filled squares; RAGE–/–, open circles. (B) EAE response in WT and Tie2RAGE mice. WT mice used were transgene-negative littermates. The mean clinical score represents a summary of two independent experiments each for WT and for Tie2RAGE. WT, filled squares; Tie2RAGE, open triangles. The standard error of the mean is given (± SEM), and P < 0.05 was considered to be statistically significant.