PMA‐induced down‐regulation of the receptor for α2‐macroglobulin in human U937 cells

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Abstract
Transcription and expression of the urokinase (uPA) receptor (uPAR) are strongly stimulated by PMA. As for uPAR, the expression of α2-MR is regulated by PMA in U937 cells. Ligand blotting experiments with the 39 kDa receptor-associated protein RAP, a ligand for α2-MR, indicated that α2-MR levels first increased and then decreased after PMA treatment. FACscan as well as immunoblotting analysis with α2-MR-specific antibodies showed an identical trend: α2-MR levels increased within the first day of treatment with PMA, decreased at later times, and totally disappeared by three days of treatment. The effect of PMA was not due to transcriptional down-regulation, as the α2-MR mRNA level did not decrease at later times. Sensitivity of U937 cells to uPA-saporin, a toxin conjugate that reguires binding to WAR for killing activity, was also markedly decreased. These results suggest that uPAR-mediated endocytosis depends on α2-MR expression.