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 microM 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.
Denholm
E M
EM
Stankus
G P
GP
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002630:Chemotactic Factors / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
C515334:CCR2 protein, human; D002630:Chemotactic Factors; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D013755:Tetradecanoylphorbol Acetate