Beta-N-acetylhexosaminidase in peripheral blood lymphocytes and monocytes in the different forms and stages of multiple sclerosis.
The activity of the acidic glycohydrolase beta-N-acetylhexosaminidase, an enzyme system normally participating in the stepwise degradation of glycoproteins, glycolipids, and proteoglycans, appears to be modulated in lymphocytes and monocytes from peripheral blood of patients affected by multiple sclerosis during different stages of the disease. In particular, a significant decrease in this enzyme activity, compared with healthy subjects, was observed in patients affected by the relapsing-remitting form both in a stable clinical status and during a relapse as well as in patients with the progressive form. The decrease in total intracellular hexosaminidase activity in lymphomonocytes of multiple sclerosis patients was accompanied by an enrichment of this activity associated with the plasma membrane fraction as demonstrated by experiments of subcellular fractionation. The analysis carried out using two synthetic substrates, 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide and its sulfate derivative, enables us to demonstrate that this accumulation is mainly due to isoenzymes with a betabeta structure, whereas lysosomal fractions confirmed the classical presence of both alphabeta and betabeta forms (hexosaminidases A and B, respectively). This was particularly evident in the plasma membrane fraction from mononuclear cells of patients with a clinical exacerbation of the disease. Considered together, these observations provide additional insight into the abnormality of peripheral blood immune cells in multiple sclerosis and may contribute to the understanding of the basic mechanisms underlying the pathological events resulting in the demyelinating process.
Orlacchio
A
A
Istituto di Clinica Neuropsichiatrica-Neurologia, University of Perugia, Italy.
Martino
S
S
Sarchielli
P
P
Gallai
V
V
Emiliani
C
C
D000328:Adult; D001773:Blood Cells / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000097:blood; D008214:Lymphocytes / Q000201:enzymology*; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology*; D009103:Multiple Sclerosis / Q000097:blood* / Q000201:enzymology* / Q000503:physiopathology; D012016:Reference Values; D013347:Subcellular Fractions / Q000201:enzymology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*
D007527:Isoenzymes; D001619:beta-N-Acetylhexosaminidases