α2-Macroglobulin synthesis by the human monocytic cell line THP-1 is differentiation state-dependent

Human α₂-macroglobulin (α₂M) is a broad spectrum proteinase inhibitor and cytokine carrier synthesized by a number of cell types including monocytes and macrophages. In this study, we report on the expression of α₂M by THP-1 cells. This monocytic cell line can be differentiated into a macrophage-like phenotype by treatment with interferon-γ (IFN-γ) or phorbol 12-myristate 13-acetate (PMA). α₂M was synthesized by THP-1 cells at a rate of 75 ng/10⁶ cells/24 h, as determined by Western blot analysis. After treating the cells with 500 U/ml of IFN-γ or with 100 ng/ml PMA, the synthesis rate increased to 219 ng/10⁶ cells/24 h and to 179 ng/10⁶ cells/24 h, respectively. The same agents also increased α₂M expression, as determined by Northern blot analysis. When the α₂M receptor antagonist, receptor associated protein (RAP), was included in the THP-1 medium, the amount of α₂M recovered in the conditioned medium increased. This result suggests that THP-1-secreted proteinases react with secreted α₂M and that the resulting complexes are catabolized by the α₂M receptor, which is also called low density lipoprotein receptor-related protein (LRP). We conclude that α₂M synthesis by THP-1 cells depends on the state of cellular differentiation. Reaction of α₂M with secreted proteinases may have minimized previous estimates of the rate of synthesis of α₂M by certain cells in culture. J. Cell. Biochem. 67:492–497, 1997. © 1997 Wiley-Liss, Inc.