title: Aberrant forms of alpha(2)-macroglobulin purified from patients with multiple sclerosis.
abstract: The biochemical properties of alpha(2)-macroglobulin were investigated in four patients with multiple sclerosis and compared to alpha(2)-macroglobulin from healthy controls. An impaired stability of alpha(2)-macroglobulin from the multiple sclerosis patients was demonstrated as a spontaneous conversion to an electrophoretic"fast" form of alpha(2)-macroglobulin upon purification and storage, with a concomitant decrease in functional capacity to inhibit proteinases. The ability to form complexes with proteinases was significantly reduced in alpha(2)-macroglobulin purified from the multiple sclerosis patients. The aberrant molecular arrangements of the protein were not due to proteinase cleavages in the bait regions of alpha(2)-macroglobulin, as demonstrated by gel electrophoresis and protein sequencing. The number of functional thiol esters, however, was reduced in alpha(2)-macroglobulin purified from the multiple sclerosis patients, an observation compatible with the impaired proteinase binding property. Furthermore, differences in isoelectric points were observed between alpha(2)-macroglobulin from the multiple sclerosis patients and alpha(2)-macroglobulin from healthy controls. The results suggest that aberrant forms of alpha(2)-macroglobulin may be present in patients with multiple sclerosis.
authors.affiliation: Department of Immunology, Umeâ University, S-901 85, Umeå, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Gunnarsson
authors.forename: T
authors.initials: T
authors.lastname: Stigbrand
authors.forename: P E
authors.initials: PE
authors.lastname: Jensen
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007525:Isoelectric Focusing; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood*; D020033:Protein Isoforms / Q000737:chemistry* / Q000302:isolation & purification; D000511:alpha-Macroglobulins / Q000737:chemistry* / Q000302:isolation & purification
chemical_list: D020033:Protein Isoforms; D000511:alpha-Macroglobulins