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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
Abstract:
Amyloidosis of the protein AA type is readily induced in mink using repeated injections of bacterial lipopolysaccharide (LPS). We have characterized splenic proteoglycans/glycosaminoglycans (PGs/GAGs) in mink during amyloidogenesis. Moderate to rich amounts of amyloid exhibiting green birefringence was demonstrated by polarization microscopy of the splenic section stained with Congo red in seven out of eight minks after 10 weeks of LPS-treatment, and a significant increase in the total amount of PGs and GAGs in AA amyloid spleens was observed (two to eight times that in unstimulated animals). Intact PGs as well as free GAGs were extracted, and heparan sulfate (HS) was the most abundant GAG in the amyloid as well as in the control spleens. The GAGs showing the most pronounced increase in the amyloid spleens was of the chondroitin sulfate/dermatan sulfate (CS/DS) type and these were extracted in the form of free GAG chains. We conclude that there is a selective enrichment of PGs/GAGs in extracted splenic amyloid in the mink, which confirms to previous observations in human amyloid as well as in other animal species, supporting their pathogenic significance in the formation of AA amyloid.
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.
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