REGULATION OF EXPRESSION OF THE LFA-1 AND P150,95 LEUKOCYTE INTEGRINS- INVOLVEMENT OF THE CD11A AND CD11C GENE PROMOTERS

Human Lymphocyte Associated Antigen-1 (LFA-1, CD11a/CD18, alpha L/beta 2) and p150,95 (CD11c/CD18, alpha X/beta 2) are cell surface alpha/be ta heterodimers that, together with Mac-1 (CD11b/CD18, alpha M/beta 2) comprise the leukocyte-restricted beta 2 subfamily of integrins. LFA- 1 is the only integrin expressed on all leukocyte lineages while p150, 95 is exclusively expressed on cells of the myeloid lineage and on act ivated B lymphocytes and natural killer cells. The expression of the l eukocyte integrins is regulated during cell activation and differentia tion by transcriptional mechanisms. To dissect the molecular basis for the tissue-restricted and developmentally regulated expression of LFA -1 and p150,95, the promoter regions of their corresponding a subunits (CD11a and CD11c) were isolated and functionally characterized. Both promoters lack TATA and CAAT boxes, but exhibit initiator-like sequenc es at their major transcriptional start sites. Transient expression of CD11a- and CD11c-based reporter gene constructs have demonstrated the involvement of both promoters in the tissue-specific expression of LF A-1 and p150,95. Furthermore, a combination of DNAse I protection expe riments and mobility band shift assays have revealed the existence of numerous DNA-protein interactions at the proximal region of both promo ters, some of which overlap with consensus binding sequences for known transcription factors and correlate with the pattern of expression of both integrins.