Leukocyte integrins which share the beta2 subunit CD18 are involved in cell adhesion to extracellular matrix and also mediate cell-cell interactions. To examine changes in integrin expression on differentiating myeloid cells the Ml, an immature murine myeloid leukemic cell line, was used. Upon stimulation with interleukin-6 (IL-6), Ml cells express surface markers, enzymes and functions of normal, mature macrophages. By FACS analysis, the alpha subunits CD11a (LFA-1) and CD11b (Mac-1) plus CD18 expression on IL-6 stimulated Ml cells were found to increase in a time dependent fashion reaching levels expressed on normal mature macrophages. The increase in integrin expression was correlated with an increase in the adhesion of IL-6 stimulated Ml cells to culture dishes. Our study shows that the expression of both the alpha and beta subunits of the leukocyte integrin family are increased during differentiation due to de-novo synthesis, similar to other markers of myeloid differentiation. Furthermore, it also shows that CD11b and CD18 are transcriptionally controlled while the expression of CD11a is post-transcriptionally regulated. Gaucher's disease is a lipid storage disorder caused by a deficiency in the enzyme glucocerebrosidase (GC). The human GC gene has been successfully transfected into murine BM stem cells which have been transplanted into lethally irradiated mice. Macrophages from these reconstituted mice, evaluated 6 months after transplantation, express the human GC protein. To develop a quick screening method for testing the retroviral vector expression of the GC gene in macrophages and to study the effect of differentiation on this gene expression, we used the Ml cell line. Transduced Ml clones with the Molony virus containing the GC cDNA were analyzed for the expression of the vector generated human GC RNA and protein before and after induction of differentiation with IL-6. Our data show that the viral LTR from the Molony virus efficiently promotes the expression of human GC RNA before and after induction of differentiation of the transducted Ml clones.
