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–/– mice and WT mice treated with sRAGE are protected against septic...
RAGE–/– mice and WT mice treated with sRAGE are protected against septic shock induced by CLP. (A) Age- and sex-matched WT and RAGE–/– mice were subjected to CLP or sham operation and were monitored for survival. WT indicates C57BL/6 ∞ 129/Sv mice. A summary of four repeated experiments is shown. One to two sham-operated mice were included in each single experiment (data not shown) and did not show overt signs of disease. WT, filled squares; RAGE–/–, open circles. (B) Therapeutic effect of sRAGE treatment. CLP was performed in age- and sex-matched C57BL/6 mice. Mice received repeated intraperitoneal injections of sRAGE or solvent (LPS-free 0.9% NaCl) immediately after CLP (150 ∝g sRAGE/mouse) and 6, 12, 24, and 36 hours thereafter (70 ∝g sRAGE/mouse). Two repeated experiments are summarized. WT treated with solvent, filled triangles; WT treated with sRAGE, asterisks. (C) Age- and sex-matched WT and Tie2RAGE mice were subjected to CLP and were monitored for survival. WT indicates transgene-negative littermates. A summary of two repeated experiments is shown. One to two sham-operated mice were included in each single experiment (data not shown) and did not show overt signs of disease. WT, filled squares; Tie2RAGE, open triangles.