Kinetics of glycosaminoglycan deposition in splenic AA amyloidosis induced in mink.

ABSTRACT

The kinetics of splenic glycosaminoglycan (GAG) expression in mink has been investigated during the course of AA amyloid induction, i.e. at 3 to 6 weeks of lipopolysaccharide (LPS) treatment. Splenic amyloid was demonstrated by means of Congo red staining in five of 19 LPS-treated mink. Chondroitin/dermatan sulfate (CS/DS), as well as heparan sulfate proteoglycans (HSPG), was extracted from amyloid and control spleens. Independently of the presence of amyloid, the total amount of splenic GAGs increased with the duration of LPS treatment, and an HSPG population was found confined to the LPS-treated spleens. The differential expression of various PG and GAG epitopes in mink spleen was investigated with the help of immunohistochemistry. The amyloid deposits were shown to contain GAG chains of CS and HS, and the core proteins of DSPG decorin and the HSPGs perlecan and agrin. Decorin and perlecan were shown in normal spleens localized to the splenic ellipsoids, an early target for AA amyloid deposition. The constitutive expression of PGs at predilection sites for amyloid deposition and their increased expression in the tissues developing amyloidosis at these early stages show that PGs are available for the formation and deposition of AA amyloid.