Cultured human monocytes synthesize and secrete alpha2-macroglobulin

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Alpha2-macroglobulin is a major human plasma proteinase inhibitor.
• Its production by peripheral blood mononuclear leukocytes is not fully understood.

Purpose of the Study:

• To investigate which subpopulations of human peripheral blood mononuclear leukocytes are responsible for alpha2-macroglobulin synthesis.
• To demonstrate de novo synthesis and release of alpha2-macroglobulin by specific leukocyte types.

Main Methods:

• Radioimmunoassay to quantify alpha2-macroglobulin levels.
• Cell culture of different mononuclear leukocyte subpopulations (unfractionated, T-enriched, B+T-enriched, glass-adherent).
• 35S-methionine labeling followed by immunoprecipitation and SDS-polyacrylamide gel electrophoresis to confirm de novo synthesis.

Main Results:

• Unfractionated mononuclear leukocytes produced significantly more alpha2-macroglobulin than T or B+T lymphocyte-enriched subpopulations.
• Glass-adherent mononuclear leukocytes (monocytes/macrophages) exhibited the highest production levels.
• De novo synthesis of alpha2-macroglobulin by cultured monocytes was confirmed.

Conclusions:

• Cells of the monocyte-macrophage lineage are the primary source of alpha2-macroglobulin in human peripheral blood leukocyte cultures.
• This study demonstrates the de novo synthesis and release of alpha2-macroglobulin by monocytes.