Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Zen, Ke; Chen, Celia X.-J.; Chen, Yi-Tien; Wilton, Rosemarie; Liu, Yuan

doi:10.4049/jimmunol.178.4.2483

Cited by 68 publications

(58 citation statements)

References 66 publications

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Section: Introductionmentioning

confidence: 88%

“…14 In contrast, Zen et al demonstrated in an in vitro assay that fMLP-induced transmigration of human neutrophils through the human intestinal epithelial cell line T84 was dependent on the presence of epithelial RAGE that bound neutrophil-expressed Mac-1. 15 These findings implicate an important role of both endothelial and neutrophil expressed RAGE in Mac-1-dependent neutrophil recruitment during inflammation.Direct in vivo observations of leukocyte recruitment in the absence of RAGE have not been reported. To prove the hypothesis that RAGE is a relevant Mac-1 ligand under in vivo conditions and dissect the contribution of endothelial and neutrophil expressed RAGE in mediating leukocyte recruitment in respect to its role as Mac-1 ligand, we studied RAGE-dependent leukocyte adhesion by intravital microscopy in an acute trauma-induced model of inflammation.…”

mentioning

confidence: 88%

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RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo

Frommhold

Kamphues

Hepper

et al. 2010

Blood

116

133

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The receptor for advanced glycation end products (RAGE) contributes to the inflammatory response in many acute and chronic diseases. In this context, RAGE has been identified as a ligand for the ␤ 2 -integrin Mac-1 under static in vitro conditions. Because intercellular adhesion molecule (ICAM)-1 also binds ␤ 2 -integrins, we studied RAGE ؊/؊ , Icam1 ؊/؊ , and RAGE ؊/؊ Icam1 ؊/؊ mice to define the relative contribution of each ligand for leukocyte adhesion in vivo. We show that trauma-induced leukocyte adhesion in cremaster muscle venules is strongly dependent on RAGE and ICAM-1 acting together in an overlapping fashion. Additional in vivo experiments in chimeric mice lacking endothelium-expressed RAGE and ICAM-1 located the adhesion defect to the endothelial compartment. Using microflow chambers coated with P-selectin, CXCL1, and soluble RAGE (sRAGE) demonstrated that sRAGE supports leukocyte adhesion under flow conditions in a Mac-1-but not LFA-1-dependent fashion. A static adhesion assay revealed that wild-type and RAGE ؊/؊ neutrophil adhesion and spreading were similar on immobilized sRAGE or fibrinogen. These observations indicate a crucial role of endotheliumexpressed RAGE as Mac-1 ligand and uncover RAGE and ICAM-1 as a new set of functionally linked adhesion molecules, which closely cooperate in mediating leukocyte adhesion during the acute traumainduced inflammatory response in vivo. IntroductionLeukocyte recruitment into inflamed tissue follows a well-defined cascade of events, beginning with the capture of free-flowing leukocytes to the vessel wall and subsequent leukocyte rolling along and adhesion to the inflamed endothelial layer. 1,2 During rolling, leukocytes get into close contact with the endothelial surface, which allows endothelial bound chemokines to interact with their specific receptors on the leukocyte surface. This triggers the activation of integrins, which leads to firm leukocyte arrest on the endothelium. In addition, integrindependent signaling events induce cytoskeletal rearrangements and cell polarization, modifications necessary in helping to prepare the attached leukocyte to spread and crawl in search for its way out of the vasculature into tissue. [2][3][4][5][6] Recent evidence has shown that the ␤ 2 -integrin Mac-1 is crucially involved in transducing Syk-dependent signaling events necessary for sustained leukocyte adhesion. [7][8][9] The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that has been identified to be a major player in chronic inflammatory conditions. 10,11 This has been mainly attributed to its strong effects on perpetuating nuclear factor-B (NF-B) activation and NF-Bdependent signaling 10,11 and its ability to induce its own expression. 10,12 Besides its function as a signaling molecule, RAGE also binds to Mac-1, which has been demonstrated under in vitro conditions. 13 In addition, a reduction of leukocyte extravasation into the inflamed peritoneal cavity was found in RAGE Ϫ/Ϫ mice after intraperitoneal application of th...

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Section: Introductionmentioning

confidence: 88%

mentioning

confidence: 88%

RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo

Frommhold

Kamphues

Hepper

et al. 2010

Blood

116

133

View full text Add to dashboard Cite

show abstract

“…Earlier RAGE has been shown to be involved in cell recruitment; RAGEdeficient mice displayed a diminished number of adherent inflammatory cells on the peritoneum after cecal ligation and puncture (CLP) (24) and a reduction in neutrophil influx in the peritoneal cavity after thioglycolate peritonitis (36). In addition, in vitro studies have suggested that RAGE is an endothelial counterreceptor for the ␤ 2 integrin Mac-1 (35,36), and that a functional interplay between RAGE and Mac-1 on leukocytes is required for HMGB1-mediated inflammatory cell recruitment (34). Our findings that RAGE Ϫ/Ϫ mice have a diminished neutrophil recruitment to the lungs during S. pneumoniae are in line with these data.…”

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

103

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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“…The viability of the monocytes was determined by trypan blue staining. An inhibitory anti-RAGE Ab was used, as previously described (18).…”

Section: Cells and Absmentioning

confidence: 99%

Role of MicroRNA-214–Targeting Phosphatase and Tensin Homolog in Advanced Glycation End Product-Induced Apoptosis Delay in Monocytes

Liu

Hou

Guo

et al. 2011

The Journal of Immunology

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Advanced glycation end products (AGEs) delay spontaneous apoptosis of monocytes and contribute to the development of inflammatory responses. However, the mechanism by which AGEs affect monocyte apoptosis is unclear. We studied the role of microRNA-214 (miR-214) and its target gene in AGE-induced monocytic apoptosis delay. Using microRNA (miRNA) microarray and stem-loop, quantitative RT-PCR assay, we studied genome-wide miRNA expression in THP-1 cells treated with or without AGEs. Significant upregulation of miR-214 was consistently observed in THP-1 and human monocytes treated with various AGEs, and AGE-induced monocytic miR-214 upregulation was likely through activation of receptor for AGEs. A striking increase in miR-214 was also detected in monocytes from patients with chronic renal failure. Luciferase reporter assay showed that miR-214 specifically binds to the phosphatase and tensin homolog (PTEN) mRNA 3′-untranslated region, implicating PTEN as a target gene of miR-214. PTEN expression is inversely correlated with miR-214 level in monocytes. Compared with normal monocytes, AGE-treated monocytes and monocytes from chronic renal failure patients exhibited lower PTEN levels and delayed apoptosis. Overexpression of pre–miR-214 led to impaired PTEN expression and delayed apoptosis of THP-1 cells, whereas knockdown of miR-214 level largely abolished AGE-induced cell survival. Our findings define a new role for miR-214–targeting PTEN in AGE-induced monocyte survival.

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Receptor for Advanced Glycation Endproducts Mediates Neutrophil Migration across Intestinal Epithelium

Cited by 68 publications

References 66 publications

RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo

RAGE and ICAM-1 cooperate in mediating leukocyte recruitment during acute inflammation in vivo

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

Role of MicroRNA-214–Targeting Phosphatase and Tensin Homolog in Advanced Glycation End Product-Induced Apoptosis Delay in Monocytes

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