IN-VIVO ANALYSIS OF MURINE SERUM SULFATE METABOLISM AND SPLENIC GLYCOSAMINOGLYCAN BIOSYNTHESIS DURING ACUTE-INFLAMMATION AND AMYLOIDOSIS

Objective. Highly sulfated glycosaminoglycans (GAG) have been demonstr ated in every form of amyloid examined to date. Based on temporal stud ies in murine amyloidogenesis heparan sulfate is deposited coincidenta lly with the amyloid protein. Our purpose was to follow in vivo GAG sy nthesis by monitoring (SO4)-S-35, incorporation during amyloidogenesis . Several necessary previously unexamined nonamyloidogenic controls we re also examined. Methods. Murine splenic amyloid was induced with lip opolysaccharide (LPS) and amyloid enhancing factor (AEF). Splenic GAG synthesis was monitored by (SO4)-S-35, incorporation. Corrections were made for alterations in SO4 metabolism which occur during inflammatio n. Results. All animals with an inflammatory reaction had a marked inc rease in GAG synthesis. Those animals receiving AEF, or AEF + LPS, had a significant increase in heparan sulfate synthesis. This was particu larly profound in the group developing amyloid (i.e., AEF + LPS). Conc lusion. Our results indicate that critical factors in amyloid depositi on include quantitative as well as qualitative changes that take place in tissue GAG synthesis. A distinct metabolic effect of AEF is demons trated for the first time.