Changes in the expression of MCP-1 receptors on monocytic THP-1 cells following differentiation to macrophages with phorbol myristate acetate

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 1995-07, Vol.7 (5), p.436-440
• Main Authors: Denholm, Elizabeth M., Stankus, Gerald P.
• Format: Article
• Language: English
• Subjects: Cell Differentiation - drug effects; Cell Line; chemokine; Chemotactic Factors - pharmacology; chemotaxis; differentiation; Humans; Macrophages - drug effects; monocyte; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; receptor; Receptors, CCR2; Receptors, Chemokine; Receptors, Cytokine - biosynthesis; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.1995.0059

Human monocytic THP-1 cells were differentiated to macrophages by incubation with 1.0 μM phorbol myristate acetate (PMA) for 1 to 18 h; cells were then assayed for the ability to migrate to MCP-1. In comparison to undifferentiated monocytes, the chemotactic response of PMA-differentiated cells to MCP-1 decreased with treatment time. This loss of the chemotactic response to MCP-1 correlated with increased in cellular enzymes characteristic of differentiated macrophages. Receptors binding assays demonstrated a parallel decrease in specific binding of MCP-1 with increased incubation with PMA. Undifferentiated monocytes had 1175 ± 387 receptors per cell with a Kd of 1.53 ± 0.35 nM. Cells differentiated to macrophages with PMA rapidly lost the ability to bind MCP-1, with a significant decrease apparent following 3 h incubation with PMA. The reduction in specific binding of MCP-1 by MΦ-THP-1 cells was due to a decrease in both receptor number and affinity; receptor number was reduced to 481 ± 106 receptors/cells with a Kd of 3.16 ± 0.7 nM on cells treated for 3 h with PMA. The demonstrated changes in receptor affinity and expression with differentiation may be a mechanism of controlling macrophage responsiveness to chemokines in inflammatory foci.