BINDING OF SOLUBLE MYELIN BASIC-PROTEIN TO VARIOUS CONFORMATIONAL FORMS OF ALPHA(2)-MACROGLOBULIN

Myelin basic protein is known to be released into the circulation foll owing traumatic injuries or demyelination within the central nervous s ystem, resulting in the generation of potentially immunogenic myelin b asic protein material. In this investigation we have studied the bindi ng of bovine and human myelin basic protein to human alpha(2)-macroglo bulin, which was found to be the only major myelin basic protein-bindi ng protein in human plasma. Myelin basic protein bound to all three co nformational forms of alpha(2)-macroglobulin studied, i.e., native alp ha(2)-macroglobulin, methylamine-treated alpha(2)-macroglobulin, and c hymotrypsin-treated alpha(2)-macroglobulin. Zinc chloride (1 mM) or 1 mM iodoacetamide partly blocked the complex formation between myelin b asic protein and alpha(2)-macroglobulin, while I mM magnesium chloride , 1 mM calcium chloride, or 1 mM EDTA had no effect on binding. Chymot rypsin and trypsin can degrade myelin basic protein to fragments which do not bind to alpha(2)-macroglobulin. However, when myelin basic pro tein was complexed with any of the conformational forms of alpha(2)-ma croglobulin, no significant release of Na[I-125]-labeled myelin basic protein occurred after proteinase treatment. The results suggest that binding of myelin basic protein to alpha(2)-macroglobulin may protect extracellular compartments in vivo from immunogenic myelin basic prote in fragments and alpha(2)-macroglobulin may participate in the specifi c clearance of myelin basic protein from the circulation. (C) 1998 Aca demic Press.