Abstract
Accumulation of fibrils composed of amyloid A in tissues resulting in displacement of normal structures and cellular dysfunction is the characteristic feature of systemic amyloidoses. Here we show that RAGE, a multiligand immunoglobulin superfamily cell surface molecule, is a receptor for the amyloidogenic form of serum amyloid A. Interactions between RAGE and amyloid A induced cellular perturbation. In a mouse model, amyloid A accumulation, evidence of cell stress and expression of RAGE were closely linked. Antagonizing RAGE suppressed cell stress and amyloid deposition in mouse spleens. These data indicate that RAGE is a potential target for inhibiting accumulation of amyloid A and for limiting cellular dysfunction induced by amyloid A.
Publication types
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amyloid / metabolism
-
Amyloidosis / metabolism*
-
Amyloidosis / pathology
-
Animals
-
Cell Line
-
Glycoproteins / metabolism
-
Glycoproteins / pharmacology
-
Heme Oxygenase (Decyclizing) / genetics
-
Heme Oxygenase-1
-
Humans
-
Interleukin-6 / genetics
-
Islet Amyloid Polypeptide
-
Macrophage Colony-Stimulating Factor / genetics
-
Membrane Proteins
-
Mice
-
Mice, Inbred C57BL
-
Monocytes / cytology
-
Monocytes / metabolism
-
NF-kappa B / metabolism
-
Rabbits
-
Receptor for Advanced Glycation End Products
-
Receptors, Immunologic / genetics
-
Receptors, Immunologic / metabolism*
-
Serum Amyloid A Protein / metabolism*
-
Silver Nitrate / metabolism
-
Silver Nitrate / pharmacology
-
Spleen / metabolism
-
Spleen / pathology
Substances
-
Amyloid
-
Glycoproteins
-
Interleukin-6
-
Islet Amyloid Polypeptide
-
Membrane Proteins
-
NF-kappa B
-
Receptor for Advanced Glycation End Products
-
Receptors, Immunologic
-
Serum Amyloid A Protein
-
amyloid enhancing factor
-
Macrophage Colony-Stimulating Factor
-
Silver Nitrate
-
HMOX1 protein, human
-
Heme Oxygenase (Decyclizing)
-
Heme Oxygenase-1
-
Hmox1 protein, mouse