title: A close ultrastructural relationship between sulfated proteoglycans and AA amyloid fibrils.
abstract: Two cationic reagents, Ruthenium red (RR) and Cuprolinic blue (CB), were used to assess the morphologic and structural relationship between sulfated proteoglycans and AA amyloid fibrils in amyloidotic spleen and liver, and in isolated fibril preparations. Amyloidotic tissue fixed in the presence of RR showed RR granules, measuring 15 to 25 nm in diameter, over areas of electrondense fibrils. In isolated fibril preparations, RR granules were specifically localized on amyloid fibrils. Amyloidotic tissue fixed in the presence of CB at 0.1 M and 0.7 M MgCl2 showed both granule and filamentous (50 to 90 nm in length) staining only over areas of amyloid fibrils. This same staining localization was also seen in isolated fibril preparations. The RR and CB granules and filaments, are believed to represent proteoglycan monomers with the glycosaminoglycan chains collapsed onto the protein core. The persistent CB staining at 0.7 M magnesium chloride suggested that highly sulfated proteoglycans were present. The glycosaminoglycan moiety has previously been identified as heparin/heparan sulphate. The intimate structural relationship between sulfated proteoglycans and AA amyloid fibrils, both in situ and in isolated fibril preparations, further suggests that these highly negatively charged molecules may have an important role in the pathogenesis of amyloidosis. Several pathogenetic scenarios are suggested.
mesh_terms: D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D005260:Female; D006025:Glycosaminoglycans / Q000032:analysis; D007211:Indoles; D008099:Liver / Q000032:analysis / Q000648:ultrastructure*; D051379:Mice; D008808:Mice, Inbred CBA; D009942:Organometallic Compounds; D011509:Proteoglycans / Q000032:analysis*; D012430:Ruthenium Red; D000685:Serum Amyloid A Protein / Q000032:analysis*; D013154:Spleen / Q000032:analysis / Q000648:ultrastructure*; D013194:Staining and Labeling; D013431:Sulfates / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D007211:Indoles; D009942:Organometallic Compounds; D011509:Proteoglycans; D000685:Serum Amyloid A Protein; D013431:Sulfates; D012430:Ruthenium Red; C015445:copper phthalocyanine