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Mast Cells Acquire Monocyte-Specific Gene Expression and Monocyte-Like Morphology by Overproduction of PU.1¹

Tomonobu Ito^*,, Chiharu Nishiyama^2,*, Makoto Nishiyama^¶, Hironori Matsuda, Keiko Maeda^*, Yushiro Akizawa^*,||, Ryoji Tsuboi, Ko Okumura^*, and Hideoki Ogawa^*,

^* Atopy (Allergy) Research Center, Department of Immunology, and Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan; Department of Dermatology, Tokyo Medical University, Tokyo, Japan; ^¶ Biotechnology Research Center, University of Tokyo, Tokyo, Japan; and ^|| Advanced Research Laboratory, Hanno Research Center, Taiho Pharmaceutical, Saitama, Japan

PU.1 is a myeloid- and lymphoid-specific transcription factor that belongs to the Ets family. Recently, we found that overproduction of PU.1 in mouse bone marrow-derived hemopoietic progenitor cells induced monocyte-specific gene expression and caused their monocyte-like morphological change. In the present study, PU.1 was overproduced by using retrovirus expression system in differentiated bone marrow-derived mast cells. By overexpression of PU.1, cell surface expression of MHC class II, CD11b, CD11c, and F4/80 was induced, accompanied by reduced expression of c-kit, a mast cell-specific marker. Morphology of PU.1-transfected cells was altered toward monocyte-like one. PU.1-overproducing cells acquired T cell stimulatory ability and showed an increase in response to LPS stimulation, while response through FcRI was markedly reduced by overproduction of PU.1. These results suggest that the differentiated mast cells still have potential to display monocytic features. When PU.1 was overproduced in a different type of mast cell, peritoneal mast cells, similar monocyte-like morphological change, and the expression of CD11b and F4/80 were induced. However, surface level of CD11c and MHC class II was not affected. These results indicate that the potential capacity to exhibit monocytic features is different between both the mast cells.

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