Mucopolysaccharides of whole human spleens in generalized amyloidosis.

Abstract

Total content and composition of mucopolysaccharides (M.P.S.) in spleens from 20 patients and 18 controls of similar ages were compared. The cases consisted of primary and secondary amyloidosis which included most predisposing diseases, as well as familial Mediterranean fever and myeloma. To discern quantitative changes, whole defatted tissue was digested with papain and pronase which left a small residue containing little hexosamine. After dialysis, sulfated M.P.S. were precipitated at pH 3.5 by excess 9-aminoacridine, and the hyaluronic acid (present in small amounts) when the pH was raised to 6.5. There was a variable increase in sulfated M.P.S. in the pathological spleens due largely to increases in heparan sulfate since it was resistant to hyaluronidase and contained glucosamine. Its proportion in the M.P.S. increased to approximately 60% in most cases, whereas although total M.P.S. declined progressively the proportion of heparan sulfate remained at 25-27% in controls. On cellulose acetate electrophoresis, M.P.S. from diseased spleens all had variable amounts of a minor constituent of lower mobility which was a heparan of low sulfate content in a case. Heparan sulfate may be implicated in the deposition of amyloid protein in insoluble microfibrils. Only heparan sulfate was found in a metachromatic residue remaining after prolonged extraction of part of a diseased spleen with CaCl2 and urea.