Gunnarsson M, Jensen P E
Department of Immunology, Umeâ University, Umeâ, S-901 85, Sweden.
Arch Biochem Biophys. 1998 Nov 15;359(2):192-8. doi: 10.1006/abbi.1998.0902.
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.
已知髓鞘碱性蛋白在中枢神经系统遭受创伤或脱髓鞘后会释放到循环系统中，从而产生具有潜在免疫原性的髓鞘碱性蛋白物质。在本研究中，我们研究了牛和人髓鞘碱性蛋白与人α2-巨球蛋白的结合情况，发现α2-巨球蛋白是人类血浆中唯一主要的髓鞘碱性蛋白结合蛋白。髓鞘碱性蛋白与所研究的α2-巨球蛋白的三种构象形式均能结合，即天然α2-巨球蛋白、甲胺处理的α2-巨球蛋白和胰凝乳蛋白酶处理的α2-巨球蛋白。氯化锌（1 mM）或1 mM碘乙酰胺部分阻断了髓鞘碱性蛋白与α2-巨球蛋白之间的复合物形成，而1 mM氯化镁、1 mM氯化钙或1 mM乙二胺四乙酸（EDTA）对结合无影响。胰凝乳蛋白酶和胰蛋白酶可将髓鞘碱性蛋白降解为不与α2-巨球蛋白结合的片段。然而，当髓鞘碱性蛋白与α2-巨球蛋白的任何一种构象形式形成复合物后，蛋白酶处理后未出现显著的Na[125I]标记的髓鞘碱性蛋白释放。结果表明，髓鞘碱性蛋白与α2-巨球蛋白的结合可能在体内保护细胞外区室免受免疫原性髓鞘碱性蛋白片段的影响，并且α2-巨球蛋白可能参与从循环系统中特异性清除髓鞘碱性蛋白。
