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

Human monocytic THP-1 cells were differentiated to macrophages by incu bation with 1.0 mu M phorbol myristate acetate (PMA) for 1 to 18 h; ce lls were then assayed for the ability to migrate to MCP-1. In comparis on to undifferentiated monocytes, the chemotactic response of PMA-diff erentiated cells to MCP-1 decreased with treatment time. This loss of the chemotactic response to MCP-1 correlated with increased in cellula r enzymes characteristic of differentiated macrophages. Receptors bind ing 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 d ifferentiated 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 ce lls was due to a decrease in both receptor number and affinity; recept or 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 change s in receptor affinity and expression with differentiation may be a me chanism of controlling macrophage responsiveness to chemokines in infl ammatory foci. (C) 1995 Academic Press Limited.