Binding of Soluble Myelin Basic Protein to Various Conformational Forms of α2-Macroglobulin

Abstract

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 α2-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 α2-macroglobulin studied, i.e., native α2-macroglobulin, methylamine-treated α2-macroglobulin, and chymotrypsin-treated α2-macroglobulin. Zinc chloride (1 mM) or 1 mM iodoacetamide partly blocked the complex formation between myelin basic protein and α2-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 α2-macroglobulin. However, when myelin basic protein was complexed with any of the conformational forms of α2-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 α2-macroglobulin may protect extracellular compartmentsin vivofrom immunogenic myelin basic protein fragments and α2-macroglobulin may participate in the specific clearance of myelin basic protein from the circulation.