M-CSF-mediated macrophage differentiation but not proliferation is correlated with increased and prolonged ERK activation

✍ Scribed by Shinya Suzu; Masateru Hiyoshi; Yuka Yoshidomi; Hideki Harada; Motohiro Takeya; Fumihiko Kimura; Kazuo Motoyoshi; Seiji Okada

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 371 KB
• Volume: 212
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.21045

✦ Synopsis

Abstract

M‐CSF is a cytokine essential for both the proliferation and differentiation of monocytes/macrophages. In this study, we established a new M‐CSF‐mediated differentiation‐inducing system, and examined how the level and duration of the activation of ERK preceded M‐CSF‐mediated differentiation. TF‐1‐fms human leukemia cells rapidly proliferated in response to M‐CSF. However, in the presence of a phorbol ester, TPA, TF‐1‐fms cells definitely switched their responsiveness to M‐CSF from proliferation to differentiation, as evidenced by a more drastic morphological change and the appearance of cells with a higher level of phagocytic activity. In TF‐1‐fms cells expressing HIV‐1 Nef protein in a conditionally active‐manner, both M‐CSF‐mediated proliferation and M‐CSF/TPA‐mediated differentiation were inhibited by the activation of Nef. The Nef‐active cells showed perturbed patterns of ERK activation. Under the proliferation‐inducing conditions (TPA‐free), parental or Nef‐inactive cells showed modest ERK activation following M‐CSF stimulation, whereas Nef‐active cells showed an earlier and transient ERK activation, despite a decrease in their proliferation rate. Under the differentiation‐inducing conditions, parental or Nef‐inactive cells showed increased and prolonged ERK activation following M‐CSF stimulation, whereas Nef‐active cells showed transient ERK activation. These results supported the idea that the increased and prolonged ERK activation led to M‐CSF‐mediated macrophage differentiation but not to proliferation. J. Cell. Physiol. 212: 519–525, 2007. © 2007 Wiley‐Liss, Inc.