ASSOCIATION OF THE EXPRESSION OF AN SR-CYCLOPHILIN WITH MYELOID CELL-DIFFERENTIATION

The role of a 150-kD SR-cyclophilin (NK-TR1) in monocyte differentiati on was investigated. Using an antipeptide monoclonal antibody, we have detected NK-TR1 in human peripheral blood monocytes and HL-60 cells. Unstimulated monocytes showed a low intracellular level of NK-TR1 prot ein that increased over 3 days of lipopolysaccharide + interferon-gamm a treatment, consistent with the kinetics of monocyte differentiation. Normal HL-60 cells also had a low level of NK-TR1 protein, and exposu re to 1.25% dimethyl sulfoxide (DMSO) resulted in a marked transient i ncrease in expression that returned to basal levels before the develop ment of granulocyte differentiation-associated biochemical changes. Ph orbol myristate acetate, a promoter of monocytic differentiation in HL -60 cells, also caused a significant increase in NK-TR1 over basal lev els. Transfection of a vector expressing NK-TR1 antisense RNA into HL- 60 cells suppressed DMSO-mediated growth arrest. In addition, the deve lopment of a more mature phenotype, as measured by expression of CD16, and the ability to reduce nitroblue tetrazoleum dye was inhibited in transfectants when compared with controls. These results are consisten t with the hypothesis that the NK-TR1 gene product is required for the progression towards a mature differentiated phenotype.