THE LEUKOCYTE INTEGRIN GENE CD11C IS TRANSCRIPTIONALLY REGULATED DURING MONOCYTE DIFFERENTIATION

The leukocyte integrins, LFA-1, Mac-1 and p150,95, are heterodimeric proteins that consist of a distinct cc and a common beta subunit. The beta subunit gene (CD18) is constitutively expressed on all leukocytes, however, the a subunit genes for LFA-1, Mac-1 and p150,95 (CD11a, CD11b and CD 11c, respectively) show cell- and developmental stage-specific expression. We investigated the regulation of the CD11c gene in the promyeloblastic leukemic cell line, HL60, following differentiation along the monocytic pathway with phorbol 12-myristate 13-acetate (PMA). The steady-state level of CD11c mRNA increased markedly over 48 hr from the undetectable level present before differentiation. The half-life of CD11c MRNA in differentiated HL60 cells was not unusually long and similar to that of CD18 mRNA found in both undifferentiated and differentiated cells which suggested that altered mRNA stability did not account for the appearance of CD11c mRNA. Nuclear run-on analysis revealed that transcriptional activation during differentiation resulted in the appearance of CD11c mRNA. Inhibition of protein synthesis by cycloheximide in undifferentiated HL60 cells did not result in transcriptional activation of the CD11c gene. However, there was a significant increase (approximately eight-fold) in the steady-state level of CD18 mRNA which was not the result of transcriptional activation. Inhibition of protein synthesis in differentiated HL60 cells did not lead to significant changes in the steady-state levels of either CD11c or CD18 mRNAs. These findings indicated that the CD11c gene is regulated by transcriptional mechanisms which require prior protein synthesis. Transcriptional activation of the CD18 gene as a result of differentiation with PMA also requires protein synthesis. Further, in the absence of protein synthesis in undifferentiated HL60 cells, post-transcriptional mechanisms stabilize CD18 mRNA.