Secretion of alpha-2-macroglobulin by human alveolar macrophages

Cultured human alveolar macrophages were shown to secrete alpha-2-macroglobulin (α2M), a potent inhibitor of bacterial and mammalian proteases. Secretion could be blocked by 2.0 µg/ml cycloheximide, an inhibitor of protein synthesis. Detection of the inhibitor was achieved by radioimmunoelectrophoresis of concentrated culture medium obtained from cells cultured in the presence of35S-methionine. In addition, concentrated culture medium was treated with antihumanα2M antiserum and antigen: antibody complexes were precipitated with protein A-bearing staphylococci. When the precipitate thus formed was dissolved in a reducing buffer and subjected to SDS electrophoresis, a single radioactive peak of about 185,000 daltons was obtained. This molecular weight corresponds closely to the molecular weight of theα2M subunit. Secretion ofα2M by alveolar macrophages may facilitate the internalization and disposal of proteolytic enzymes in the alveolar microenvironment, and thus play an important role in the defense of the lung.