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. IntroductionThe adaptive and the innate immune systems are both capable of initiating inflammation. The two are interconnected at several levels, including the synthesis and action of cytokines, molecules regulating cell-cell interactions, and the activation of transcription factors (1-9). While the molecular events leading to activation of the immune response are well understood, less is known about factors that perpetuate inflammation. One mechanism considered central in the cross-talk between the innate and adaptive immune systems is the redox-dependent activation of the transcription factor NF-κB (1, 4, 9-13). Members of the NF-κB family control the initiation of inflammation by regulating expression of leukocyte adhesion molecules, cytokines, and other factors (10-13), but are also central in terminating inflammation (14)(15)(16)(17)(18). This leaves unanswered the question of the perpetuation of inflammation of the adaptive and innate immune responses.Recently, studies of the receptor for advanced glycation end products (RAGE) (19-23), a member of the immunoglobulin superfamily (23) whose gene is located in the vicinity of the MHC

Binding activity for nuclear factor kappa B (NF B) consensus probes was studied in nuclear extracts from peripheral blood mononuclear cells of 15 septic patients (

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. IntroductionThe adaptive and the innate immune systems are both capable of initiating inflammation. The two are interconnected at several levels, including the synthesis and action of cytokines, molecules regulating cell-cell interactions, and the activation of transcription factors (1-9). While the molecular events leading to activation of the immune response are well understood, less is known about factors that perpetuate inflammation. One mechanism considered central in the cross-talk between the innate and adaptive immune systems is the redox-dependent activation of the transcription factor NF-κB (1, 4, 9-13). Members of the NF-κB family control the initiation of inflammation by regulating expression of leukocyte adhesion molecules, cytokines, and other factors (10-13), but are also central in terminating inflammation (14)(15)(16)(17)(18). This leaves unanswered the question of the perpetuation of inflammation of the adaptive and innate immune responses.Recently, studies of the receptor for advanced glycation end products (RAGE) (19-23), a member of the immunoglobulin superfamily (23) whose gene is located in the vicinity of the MHC

No abstract

No abstract