Binding of soluble myelin basic protein to various conformational forms of alpha2-macroglobulin.
Myelin basic protein is known to be released into the circulation following traumatic injuries or demyelination within the central nervous system, resulting in the generation of potentially immunogenic myelin basic protein material. In this investigation we have studied the binding of bovine and human myelin basic protein to human alpha2-macroglobulin, which was found to be the only major myelin basic protein-binding protein in human plasma. Myelin basic protein bound to all three conformational forms of alpha2-macroglobulin studied, i.e., native alpha2-macroglobulin, methylamine-treated alpha2-macroglobulin, and chymotrypsin-treated alpha2-macroglobulin. Zinc chloride (1 mM) or 1 mM iodoacetamide partly blocked the complex formation between myelin basic protein and alpha2-macroglobulin, while 1 mM magnesium chloride, 1 mM calcium chloride, or 1 mM EDTA had no effect on binding. Chymotrypsin and trypsin can degrade myelin basic protein to fragments which do not bind to alpha2-macroglobulin. However, when myelin basic protein was complexed with any of the conformational forms of alpha2-macroglobulin, no significant release of Na[125I]-labeled myelin basic protein occurred after proteinase treatment. The results suggest that binding of myelin basic protein to alpha2-macroglobulin may protect extracellular compartments in vivo from immunogenic myelin basic protein fragments and alpha2-macroglobulin may participate in the specific clearance of myelin basic protein from the circulation.
Gunnarsson
M
M
Department of Immunology, Umeâ University, Umeâ, S-901 85, Sweden.
Jensen
P E
PE
D001798:Blood Proteins / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D007460:Iodoacetamide / Q000494:pharmacology; D015636:Magnesium Chloride / Q000494:pharmacology; D004676:Myelin Basic Protein / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D011489:Protein Denaturation; D012995:Solubility; D017967:Zinc Compounds / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000737:chemistry / Q000378:metabolism*
D001798:Blood Proteins; D002712:Chlorides; D004676:Myelin Basic Protein; D017967:Zinc Compounds; D000511:alpha-Macroglobulins; D015636:Magnesium Chloride; C016837:zinc chloride; D004492:Edetic Acid; D010450:Endopeptidases; D003545:Cysteine; D002122:Calcium Chloride; D007460:Iodoacetamide