ALPHA(2)-MACROGLOBULIN SYNTHESIS BY THE HUMAN MONOCYTIC CELL-LINE THP-1 IS DIFFERENTIATION STATE-DEPENDENT

Human alpha(2)-macroglobulin (alpha(2)M) is a broad spectrum proteinas e 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(2)M by THP-1 cells. This monocytic cell line can b e differentiated into a macrophage-like phenotype by treatment with in terferon-gamma (IFN-gamma) or phorbol 12-myristate 13-acetate (PMA). a lpha(2)M 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 cell s 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(2)M expression, as determined by Northern blot analysis. When the alpha(2)M receptor anta gonist, receptor associated protein (RAP), was included in the THP-1 m edium, the amount of alpha(2)M recovered in the conditioned medium inc reased. Th is result suggests that THP-1-secreted proteinases react wi th secreted alpha(2)M and that the resulting complexes are catabolized by the alpha(2)M receptor, which is also called low density lipoprote in receptor-related protein (LRP). We conclude that alpha(2)M synthesi s by THP-1 cells depends on the state of cellular differentiation. Rea ction of alpha(2)M With secreted proteinases may have minimized previo us estimates of the rate of synthesis of alpha(2)M by certain cells in culture. J. Cell. Biochem. 67:492-497, 1997. (C) 1997 Wiley-Liss, Inc .