A temporal and ultrastructural relationship between heparan sulfate proteoglycans and AA amyloid in experimental amyloidosis.
Previous histochemical studies have suggested a close temporal relationship between the deposition of highly sulfated glycosaminoglycans (GAGs) and amyloid during experimental AA amyloidosis. In the present investigation, we extended these initial observations by using specific immunocytochemical probes to analyze the temporal and ultrastructural relationship between heparan sulfate proteoglycan (HSPG) accumulation and amyloid deposition in a mouse model of AA amyloidosis. Antibodies against the basement membrane-derived HSPG (either protein core or GAG chains) demonstrated a virtually concurrent deposition of HSPGs and amyloid in specific tissue sites regardless of the organ involved (spleen or liver) or the induction protocol used (amyloid enhancing factor + silver nitrate, or daily azocasein injections). Polyclonal antibodies to AA amyloid protein and amyloid P component also demonstrated co-localization to sites of HSPG deposition in amyloid sites, whereas no positive immunostaining was observed in these locales with a polyclonal antibody to the protein core of a dermatan sulfate proteoglycan (known as "decorin"). Immunogold labeling of HSPGs (either protein core or GAG chains) in amyloidotic mouse spleen or liver revealed specific localization of HSPGs to amyloid fibrils. In the liver, heparan sulfate GAGs were also immunolocalized to the lysosomal compartment of hepatocytes and/or Kupffer cells adjacent to sites of amyloid deposition, suggesting that these cells are involved in HSPG production and/or degradation. The close temporal and ultrastructural relationship between HSPGs and AA amyloid further implies an important role for HSPGs during the initial stages of AA amyloidosis.
Department of Pathology, University of Washington, Seattle 98195.
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Snow
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Bramson
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Mar
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Wight
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Kisilevsky
D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006497:Heparan Sulfate / Q000032:analysis*; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008808:Mice, Inbred CBA; D008854:Microscopy, Electron; D000685:Serum Amyloid A Protein / Q000032:analysis*; D000683:Serum Amyloid P-Component / Q000378:metabolism; D013154:Spleen / Q000737:chemistry / Q000648:ultrastructure
D006497:Heparan Sulfate; D000685:Serum Amyloid A Protein; D000683:Serum Amyloid P-Component