Dissociation of early and late markers of murine myeloid differentiation by interferon‐gamma and interleukin‐6

Publisher Website
Google Scholar
Abstract
Murine myeloid leukemia M1 cells undergo terminal differentiation to mature macrophages after stimulation with interleukin‐6 (IL‐6). This process can be monitored by measuring the expression of early markers such as the high affinity receptor for monomeric IgG2a (FcγRI) and la antigen followed by late markers such as lysozyme production and finally morphological changes from blast cells to mature macrophages. The same early markers that are expressed on M1 cells after induction with IL‐6 are also expressed on monocytic cells after activation with interferon‐γ (IFNγ). We used IL‐6 and IFNγ to investigate whether the early stages of M1 cell differentiation could be accomplished without commitment of the cells to terminal differentiation. Cytofluorometry shows that the expression of the same early differentiation markers (FcγRI and la antigen) that are inducible by IL‐6 on M1 cells can be induced by IFNγ as well. However, stimulation with IFNγ, in contrast to IL‐6, does not induce the late differentiation markers such as lysozyme production, phagocytic activity, and morphological changes. Northern analysis supports these findings in that expression of FcγRI mRNA is induced by either cytokine, whereas expression of mRNA for lysozyme is inducible by IL‐6 only. Nuclear run‐on analysis reveals that the changes in steady state mRNA levels of both FcγRI and lysozyme are regulated by a transcriptional mechanism. These data suggest that early stages in the process of myeloid differentiation can be separately induced by IFNγ and thus are independent from the later events induced by IL‐6.