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Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2390-2395
Matrix Metalloproteinase-9 Production, a Newly Identified Function of
Mast Cell Progenitors, Is Downregulated by c-kit Receptor
Activation
Akane Tanaka,
Katsuhiko Arai,
Yukihiko Kitamura, and
Hiroshi Matsuda
From the Departments of Veterinary Clinic and Tissue Physiology,
Faculty of Agriculture, Tokyo University of Agriculture and Technology,
Tokyo, Japan; and the Department of Pathology, Osaka University School
of Medicine, Osaka, Japan.
Mast cell precursors invade from the peripheral blood into local
tissues where they differentiate to their mature phenotypes. However,
the mechanism of this migration process has been unclear. We clearly
demonstrated here the production and release of matrix metalloproteinase-9 (MMP-9), a matrix-degrading enzyme necessary for
leukocyte transmigration, by interleukin-3-dependent mouse mast cell
progenitors: bone marrow-derived cultured mast cells and IC-2 mast
cells. Because several interleukin-3-independent mast cell lines with
active mutations in the c-kit gene did not release MMP-9, the
possible involvement of c-kit receptor activation in
downregulation of MMP-9 production was predicted. c-kit
receptor activation by stem cell factor led to a significant decrease
in MMP-9 production of cultured mast cells and IC-2 mast cells
transfected with the c-kit gene. Thus, the present results
suggest that mast cell precursors are able to produce MMP-9, which may
be essential for mast cell migration into tissues, and that stem cell
factor may downregulate the MMP-9 production, resulting in engagement of mast cells to matrix components.
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