AA glomerular amyloid. An ultrastructural immunogold study of the colocalization of heparan sulphate proteoglycan and P component with amyloid fibrils together with changes in distribution of type IV collagen and fibronectin.
An ultrastructural investigation was undertaken on paraformaldehyde-fixed Lowicryl resin-embedded human kidneys of three patients with AA amyloidosis to investigate the association of various basement membrane components with amyloid fibrils. An immunogold technique was used and antibodies to serum amyloid A, heparan sulphate proteoglycan, type IV collagen, P component, and fibronectin were applied to human normal and amyloid glomeruli. The amyloid was identified as AA, and P component was shown to be intimately associated with the fibrils. In addition, heparan sulphate proteoglycan was associated with amyloid in all subendothelial, subepithelial and intramembranous glomerular basement membrane deposits, and those throughout the mesangial matrix. This contrasted with the distribution of the proteoglycan in the normal glomerulus where it was found predominantly on the epithelial aspect of the basement membrane and only in the more peripheral regions of the mesangium. The accumulation of heparan sulphate proteoglycan with amyloid resulted in a marked increase in its amount in the glomeruli. The amyloid deposits contained little or no type IV collagen or fibronectin. These findings demonstrate a strong association of heparan sulphate proteoglycan with amyloid and suggest different roles for the various glomerular basement membrane components in amyloidogenesis.
Moss
J
J
Department of Histopathology, Charing Cross and Westminster Medical School, London, UK.
Shore
I
I
Woodrow
D
D
D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology*; D001485:Basement Membrane / Q000737:chemistry / Q000648:ultrastructure; D003094:Collagen / Q000032:analysis; D005353:Fibronectins / Q000032:analysis; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000032:analysis*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000737:chemistry* / Q000648:ultrastructure*; D011509:Proteoglycans / Q000032:analysis*; D000685:Serum Amyloid A Protein / Q000032:analysis*; D000683:Serum Amyloid P-Component / Q000032:analysis*
D003094:Collagen; D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans; D000685:Serum Amyloid A Protein; D000683:Serum Amyloid P-Component