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The receptor for advanced glycation end products (RAGE) is a central mediator of the interaction of AGE-beta2microglobulin with human mononuclear phagocytes via an oxidant-sensitive pathway. Implications for the pathogenesis of dialysis-related amyloidosis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Miyata, Toshio Hori, Osamu Zhang, Jinghua Ferran, Luis J. Iida, Yoshitaka Schmidt, Ann Marie |
| Copyright Year | 1996 |
| Abstract | An important component of amyloid fibrils in dialysis-related amyloidosis is a form of beta2microglobulin modified with advanced glycation end products (AGEs) of the Maillard reaction, known as AGE-beta2M. We demonstrate here that the interaction of AGE-beta2M with mononuclear phagocytes (MPs), cells important in the pathogenesis of the inflammatory arthropathy of dialysis-related amyloidosis, is mediated by the receptor for AGEs, or RAGE. 125I-AGE-beta2M bound to immobilized RAGE or to MPs in a specific, dose-dependent manner (Kd approximately 53.5 and approximately 81.6 nM, respectively), a process inhibited in the presence of RAGE blockade. AGE-beta2M-mediated monocyte chemotaxis was prevented by excess sRAGE or anti-RAGE IgG. Induction of tumor necrosis factor-alpha (TNF) expression by MPs exposed to AGE-beta2M resulted from engagement of RAGE, as appearances of TNF transcripts and TNF antigen release into culture supernatants were prevented by addition of sRAGE, a process mediated, at least in part, by oxidant stress. AGE-beta2M reduced cytochrome c and the elaboration of TNF by MPs was inhibited by N-acetylcysteine. Consistent with these data, immunohistochemical studies of AGE-laden amyloid deposits of a long-term hemodialysis patient revealed positive staining for RAGE in the MPs infiltrating these lesions. These data indicate that RAGE is a central binding site for AGEs formed in vivo and suggest that AGE-beta2M-MP-RAGE interaction likely contributes to the initiation of an inflammatory response in amyloid deposits of long-term hemodialysis patients, a process which may ultimately lead to bone and joint destruction. |
| File Format | PDF HTM / HTML |
| DOI | 10.1172/JCI118889 |
| Alternate Webpage(s) | https://kuscholarworks.ku.edu/bitstream/handle/1808/17870/YanShirley_JCI_98(5)1088.pdf?isAllowed=y&sequence=1 |
| Alternate Webpage(s) | http://dm5migu4zj3pb.cloudfront.net/manuscripts/118000/118889/JCI96118889.pdf |
| PubMed reference number | 8787669 |
| Alternate Webpage(s) | https://doi.org/10.1172/JCI118889 |
| Journal | Medline |
| Volume Number | 98 |
| Issue Number | 5 |
| Journal | The Journal of clinical investigation |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
