CHARACTERIZATION OF GROWTH-INHIBITORY ACTIVITIES ASSOCIATED WITH AN ALPHA-MACROGLOBULIN OF MICE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (5) , 1788-1797
Abstract
An .alpha.-macroglobulin (AMG) of similar size and proteinase-binding activity as those of human .alpha.2-macroglobulin was purified to homogeneity from mouse plasma. Even after additional purification steps, AMG still retained a growth-inhibitory activity and a more complex subunit structure than did human .alpha.2-macroglobulin. AMG could inhibit the DNA synthesis of all types of murine tumor cells tested in vitro. This activity was cytostatic, dose-dependent and unaffected by the serum concentration in culture. Because this inhibitory activity was resistant to heat, pH 3 and methylamine, it was apparently unrelated to the proteinase-binding activity which is labile to all these treatments. In contrast to the proteinase-binding activity, the inhibitory activity could be partially removed from AMG by acid dialysis. Gel filtration of the dialysate yielded 2 fractions (MW 12,000 and 1000-5000) which potently inhibited murine tumor cells but stimulated both the B- and T-lymphocyte reactivities to mitogens in vitro. The growth-inhibitory activities in these fractions were resistant to digestions by chymotrypsin, RNase and DNase. AMG apparently did not inhibit tumor growth by virtue of its proteinase-binding activity; it may have inhibited tumor cells via the small biomediators it carries.