CHANGES IN THE EXPRESSION OF MCP-1 RECEPTORS ON MONOCYTIC THP-1 CELLS FOLLOWING DIFFERENTIATION TO MACROPHAGES WITH PHORBOL-MYRISTATE ACETATE

Human monocytic THP-1 cells were differentiated to macrophages by incubation with 1.0 mu M 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 M phi-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. (C) 1995 Academic Press Limited.