In vivo analysis of murine serum sulfate metabolism and splenic glycosaminoglycan biosynthesis during acute inflammation and amyloidosis.
OBJECTIVE
Highly sulfated glycosaminoglycans (GAG) have been demonstrated in every form of amyloid examined to date. Based on temporal studies in murine amyloidogenesis heparan sulfate is deposited coincidentally with the amyloid protein. Our purpose was to follow in vivo GAG synthesis by monitoring 35SO4 incorporation during amyloidogenesis. Several necessary previously unexamined nonamyloidogenic controls were also examined.


METHODS
Murine splenic amyloid was induced with lipopolysaccharide (LPS) and amyloid enhancing factor (AEF). Splenic GAG synthesis was monitored by 35SO4 incorporation. Corrections were made for alterations in SO4 metabolism which occur during inflammation.


RESULTS
All animals with an inflammatory reaction had a marked increase in GAG synthesis. Those animals receiving AEF, or AEF+LPS, had a significant increase in heparan sulfate synthesis. This was particularly profound in the group developing amyloid (i.e., AEF+LPS).


CONCLUSIONS
Our results indicate that critical factors in amyloid deposition include quantitative as well as qualitative changes that take place in tissue GAG synthesis. A distinct metabolic effect of AEF is demonstrated for the first time.
Lyon
A W
AW
Department of Pathology, Queen's University, Kingston, ON, Canada.
Anastassiades
T
T
Kisilevsky
R
R
D000208:Acute Disease; D000682:Amyloid / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism*; D000818:Animals; D006023:Glycoproteins / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006497:Heparan Sulfate / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D011498:Protein Precursors / Q000378:metabolism; D013154:Spleen / Q000378:metabolism*; D013158:Splenic Diseases / Q000378:metabolism*; D013431:Sulfates / Q000097:blood*; D013462:Sulfur Radioisotopes
D000682:Amyloid; D006023:Glycoproteins; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; D008070:Lipopolysaccharides; D011498:Protein Precursors; D013431:Sulfates; D013462:Sulfur Radioisotopes; C046748:amyloid enhancing factor