alpha 2-Macroglobulin synthesis by the human monocytic cell line THP-1 is differentiation state-dependent

Human alpha 2-macroglobulin (alpha 2M) 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 alpha 2M by THP-1 cells. This monocytic cell line can be differentiated into a macrophage-like phenotype by treatment with interferon-gamma (IFN-gamma) or phorbol 12-myristate 13-acetate (PMA). alpha 2M was synthesized by THP-1 cells at a rate of 75 ng/10(6) cells/24 h, as determined by Western blot analysis. After treating the cells with 500 U/ml of IFN-gamma or with 100 ng/ml PMA, the synthesis rate increased to 219 ng/10(6) cells/24 h and to 179 ng/10(6) cells/24 h, respectively. The same agents also increased alpha 2M expression, as determined by Northern blot analysis. When the alpha 2M receptor antagonist, receptor associated protein (RAP), was included in the THP-1 medium, the amount of alpha 2M recovered in the conditioned medium increased. This result suggests that THP-1-secreted proteinases react with secreted alpha 2M and that the resulting complexes are catabolized by the alpha 2M receptor, which is also called low density lipoprotein receptor-related protein (LRP). We conclude that alpha 2M synthesis by THP-1 cells depends on the state of cellular differentiation. Reaction of alpha 2M with secreted proteinases may have minimized previous estimates of the rate of synthesis of alpha 2M by certain cells in culture.