科研之友
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摘要
Radioiodinated transforming growth factor-beta-1 (TGF-beta-1) bound to the plasma proteinase inhibitor, alpha-2-macroglobulin (alpha-2-M), as determined by chromatography on Superose-6 and native polyacrylamide gel electrophoresis. When alpha-2M conformation change was induced with methylamine I-125-beta-1 binding significantly increased. Intravenously injected I-125-TGF-beta-1 cleared from the circulation of mice rapidly at first; however, intravascular radioactivity stabilized near 20% of the initial level. At necropsy, radioactivity was recovered predominantly in the liver (65%); however, the density of radioactivity (disintegrations per minute/g organ wt) was highest in the lungs. Markedly different results were obtained with purified I-125-TGF-beta-1-alpha-2M-methylamine complex. Clearance of the complex occurred as a first-order process with a t1/2 of 4 min. Greater than 90% of the radioactivity was recovered in the liver. The clearance and distribution of I-125-TGF-beta-1-alpha-2M-methylamine were equivalent to those observed with I-125-alpha-2M-methylamine and I-125-alpha-2M-trypsin. The latter two radioligands clear via specific alpha-2-M receptors in the liver. Large molar excesses of alpha-2-M-trypsin or alpha-2-M-methylamine competed with I-125-TGF-beta-1-alpha-2M-methylamine for plasma clearance. Native alpha-2-M, which does not bind to the alpha-2-M receptor, did not compete. The receptor binding domain of alpha-2-M-methylamine was blocked by chemical modification or enzyme treatment. The resulting alpha-2-M preparations still bound I-125-TGF-beta-1; however, the complexes did not clear when injected intravenously in mice. The studies presented here demonstrate that alpha-2-M can mediate the plasma clearance of a growth factor via the alpha-2-M receptor system. We propose that alpha-2-M receptor, and proteinases may function as a concerted system to regulate TGF-beta-1 activity and the activity of related factors in vivo.
- 出版日期1991-1
