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α 2 ‐Macroglobulin synthesis by the human monocytic cell line THP‐1 is differentiation state‐dependent
Author(s) -
Lysiak Jeffrey J.,
Hussaini Isa M.,
Gonias Steven L.
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19971215)67:4<492::aid-jcb7>3.0.co;2-n
Subject(s) - thp1 cell line , cell culture , microbiology and biotechnology , receptor , western blot , monocyte , northern blot , u937 cell , phorbol , chemistry , biology , biochemistry , signal transduction , complementary dna , protein kinase c , immunology , gene , genetics
Human α 2 ‐macroglobulin (α 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 α 2 M 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). α 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‐γ 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 α 2 M expression, as determined by Northern blot analysis. When the α 2 M receptor antagonist, receptor associated protein (RAP), was included in the THP‐1 medium, the amount of α 2 M recovered in the conditioned medium increased. This result suggests that THP‐1‐secreted proteinases react with secreted α 2 M and that the resulting complexes are catabolized by the α 2 M receptor, which is also called low density lipoprotein receptor‐related protein (LRP). We conclude that α 2 M synthesis by THP‐1 cells depends on the state of cellular differentiation. Reaction of α 2 M with secreted proteinases may have minimized previous estimates of the rate of synthesis of α 2 M by certain cells in culture. J. Cell. Biochem. 67:492–497, 1997. © 1997 Wiley‐Liss, Inc.