CD32C (FC-GAMMA-RIIC) MESSENGER-RNA EXPRESSION AND REGULATION

The cell surface expression of the CD32 receptors for the Fc portion o f immunoglobulin G (Fcgamma RII-CD32) is regulated by agents such as p horbol esters (PMA) and cytokines. In this study, we investigated the effects of PMA and interferon-gamma (IFN-gamma) on the expression of C D32C mRNA in U937 cells. When U937 (CD32+) cells are incubated with ei ther PMA or IFN-gamma a significant enhancement of CD32C mRNA expressi on is observed with maximum enhancement at 18 hrs post-PMA and IFN-gam ma addition. The addition of actinomycin D (ActD), a transcriptional i nhibitor, together with either PMA or IFN-gamma diminishes the enhance d levels of CD32C mRNA to the basal levels, indicating that transcript ional regulation is involved in this modulatory process. The addition of cyclohexamide (CX), a protein synthesis inhibitor, to cultures unde rgoing stimulation with either PMA or IFN-gamma, increased the levels of CD32C mRNA synthesis suggesting that regulatory degradation protein s may be involved. The PMA and IFN-gamma stimulated CD32C mRNA is degr aded within 2 hr post-stimulation and this degradation is delayed by t he inhibition of de novo protein synthesis. These results, taken toget her with our previous studies of CD32A mRNA regulation in U937 cells s timulated with PMA, indicate that both the CD32A and C isomer mRNAs ar e rapidily degraded; however, CD32A and C isomer mRNAs are differentia lly regulated. At the optimal PMA dose, the time of mRNA stimulation o f CD32A and C mRNA varies and the addition of CX to U937 cells togethe r with PMA enhanced the levels of CD32C mRNA but had no effect on CD32 A mRNA levels. These results imply that the differential regulation of the two CD32 isomers may result in differential function.