Uptake and degradation of α2-macroglobulin-protease complexes in human cells in culture

Serum components, present intracellularly in cultured human fibroblasts, were identified as α₂-macroglobulin (α₂M), albumin, α₁-trypsin inhibitor, hemopexin and transferrin, among others. These components were shown to be taken up from the culture medium. Kinetic analysis of the uptake of α₂M-trypsin complexes by the cells showed the uptake to be of a high affinity mechanism (K_M = 6 × 10⁻⁸ M α₂M in the medium), with a high rate of internalization (V_max=1.03 × 10⁶ molecules α₂M/cell and α₂M per hour). The intracellular degradation of α₂M is rapid, as judged by the half-life of 1.6 h. Virus-transformed or tumor-derived cell lines showed low or undetectable levels of α₂M. The possible physiological significance of the described phenomena is discussed in relation to the in vivo situation.