Systemic and local high mobility group box 1 concentrations during severe infection

Zoelen, Marieke A. D. van; Laterre, Pierre‐François; Veen, Suzanne Q. van; Till, J. W. Olivier van; Wittebole, Xavier; Bresser, Paul; Tanck, Michael W.T.; Dugernier, Thierry; Ishizaka, Akitoshi; Boermeester, Marja A.; Poll, Tom van der

doi:10.1097/00003246-200712000-00019

Cited by 33 publications

(24 citation statements)

References 33 publications

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“…From these ligands, HMGB1 and S100 family members are likely to be released in this pneumonia model. Previously, we showed that HMGB1 levels were higher in BALF from patients with pneumonia at the site of infection compared with BALF from healthy controls (46). From the S100 family members, definitive evidence for binding to RAGE has only been deduced for S100A12, S100B, and S100P (9 -11).…”

Section: Discussionmentioning

confidence: 99%

The Receptor for Advanced Glycation End Products Impairs Host Defense in Pneumococcal Pneumonia

Zoelen

Schouten

Vos

et al. 2009

The Journal of Immunology

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102

126

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Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. The receptor for advanced glycation end products (RAGE) is a multiligand receptor that is expressed ubiquitously in the lungs. Engagement of RAGE leads to activation of multiple intracellular signaling pathways, including NF-κB and subsequent transcription of several proinflammatory mediators. To determine the role of RAGE in the innate immune response to S. pneumoniae pneumonia, RAGE-deficient (RAGE−/−) and wild-type mice were intranasally inoculated with S. pneumoniae. S. pneumoniae pneumonia resulted in an up-regulation of constitutively present RAGE expression in lung tissue, especially in the interalveolar septae. RAGE−/− mice showed an improved survival, which was accompanied by a lower bacterial load in the lungs at 16 h and a decreased dissemination of the bacteria to blood and spleen at 16 and 48 h after inoculation. RAGE−/− macrophages showed an improved killing capacity of S. pneumoniae in vitro. Lung inflammation was attenuated in RAGE−/− mice at 48 h after inoculation, as indicated by histopathology and cytokine/chemokine levels. Neutrophil migration to the lungs was mitigated in the RAGE−/− mice. In addition, in RAGE−/− mice, activation of coagulation was diminished. Additional studies examining the effect of RAGE deficiency on the early (6-h) inflammatory response to S. pneumoniae did not reveal an early accelerated or enhanced immune response. These data suggest that RAGE plays a detrimental role in the host response to S. pneumoniae pneumonia by facilitating the bacterial growth and dissemination and concurrently enhancing the pulmonary inflammatory and procoagulant response.

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Section: Discussionmentioning

confidence: 99%

The Receptor for Advanced Glycation End Products Impairs Host Defense in Pneumococcal Pneumonia

Zoelen

Schouten

Vos

et al. 2009

The Journal of Immunology

Self Cite

102

126

View full text Add to dashboard Cite

show abstract

“…Furthermore, the fi nding that defi ciency of RAGE in general was associated with an exaggerated host response during E. coli sepsis [42] on the one hand, and with an attenuated infl ammatory response and better survival in (other) sterile models of intraperitoneal injection of LPS derived from E. coli [42,44] on the other hand, suggests that although RAGE is involved in the immune reaction to E. coli, this function can be compensated for by other receptors in the presence of a growing bacterial load. Th e high-affi nity RAGE ligand, HMGB1, is secreted into the circulation systemically during clinical sepsis [16][17][18] as well as in our experimental sepsis model of E. coli [43]. Importantly, HMGB1 has been shown to transduce cellular signals in vitro and in vivo by interacting with at least three other receptors, i.e., TLR2, TLR4 and TLR9 when HMGB1 is complexed with CPG DNA [24,44,45].…”

Section: Rage During Abdominal Sepsismentioning

confidence: 89%

“…Levels of the high-affi nity RAGE ligand, HMGB1, were higher in BAL fl uid from patients with pneumonia compared to BAL fl uid from healthy controls [17]. In experimentally induced pneumococcal pneumonia, the presence of RAGE was detrimental: Mice lacking RAGE had a better survival rate together with a lower pulmonary bacterial load and decreased dissemination of S. pneumoniae to blood and spleen compared to wildtype mice [39].…”

Section: Role Of Rage In Pneumonia Caused By Diff Erent Pathogensmentioning

confidence: 93%

“…Most investigations on HMGB1 and infection involve sepsis, the second leading cause of death in non-coronary intensive care units (ICUs) and the 10 th leading cause of death overall. Patients with severe sepsis display elevated circulating HMGB1 levels [15][16][17] and HMGB1 is predominantly released at the site of infection; patients with pneumonia and those with peritonitis showed increased concen trations in fl uid obtained from the bronchoalveolar space and abdomen, respectively [17]. In an animal model of CLP-induced sepsis, the kinetics of HMGB1 secretion in vivo was delayed and more sustained when compared with the release of pro-infl ammatory cytokines, like TNF-α, IL-1β and IL-6 [18,19].…”

Section: Hmgb1mentioning

confidence: 99%

“…Th ese data indicate a critical role of this cytosolic portion in transducing the signal from the cell surface to the nucleus. The damage-associated molecular patterns (DAMPs), high-mobility group box 1 (HMGB1) and S100A12, are released during infection ( [15,17], and unpublished data) and bind to and activate RAGE. It has to be determined whether other S100 proteins and other DAMPs are RAGE ligands (indicated as purple shapes) released during infection.…”

Section: Rage: a Signal Transducing Receptormentioning

confidence: 99%

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