Characterization of proteoglycans and glycosaminoglycans in splenic AA amyloid induced in mink

T N Wien1, L A Omtvedt, T Landsverk

  • 1Centre for Rheumatic Diseases/Institute of Immunology, The National Hospital, N-0027 Oslo, Norway. t.n.wien@klinmed.uio.no

Insights

AA amyloidosis in mink, induced by bacterial lipopolysaccharide (LPS), shows increased splenic proteoglycans/glycosaminoglycans (PGs/GAGs). Chondroitin sulfate/dermatan sulfate (CS/DS) GAGs significantly increased, suggesting their role in AA amyloid formation.

Area of Science:

  • Biochemistry
  • Pathology
  • Immunology

Background:

  • AA amyloidosis is a protein misfolding disease.
  • Proteoglycans/glycosaminoglycans (PGs/GAGs) are implicated in amyloidogenesis.
  • Animal models are crucial for studying amyloid diseases.

Purpose of the Study:

  • To characterize splenic PGs/GAGs during AA amyloidosis in mink.
  • To investigate the role of PGs/GAGs in AA amyloid formation.
  • To compare findings with human and other animal amyloidosis models.

Main Methods:

  • Induction of AA amyloidosis in mink using bacterial lipopolysaccharide (LPS).
  • Polarization microscopy of splenic sections stained with Congo red.
  • Extraction and biochemical analysis of splenic PGs/GAGs.

Main Results:

  • AA amyloid was successfully induced in mink spleens.
  • A significant increase (2-8 fold) in total splenic PGs/GAGs was observed in amyloidotic spleens.
  • Heparan sulfate (HS) was the most abundant GAG, while chondroitin sulfate/dermatan sulfate (CS/DS) showed the most pronounced increase.

Conclusions:

  • Selective enrichment of PGs/GAGs occurs in splenic AA amyloid in mink.
  • Increased CS/DS GAGs, particularly free chains, are associated with AA amyloid formation.
  • These findings support the pathogenic significance of PGs/GAGs in AA amyloidosis across species.