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

✍ Scribed by Jeffrey J. Lysiak; Isa M. Hussaini; Steven L. Gonias

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 244 KB
• Volume: 67
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19971215)67:4<492::aid-jcb7>3.0.co;2-n

✦ Synopsis

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