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Blood, Vol. 93 No. 10 (May 15), 1999:
pp. 3473-3486
A Novel Function for Transforming Growth Factor- 1:
Upregulation of the Expression and the IgE-Independent Extracellular
Release of a Mucosal Mast Cell Granule-Specific -Chymase, Mouse Mast
Cell Protease-1
Hugh R.P. Miller,
Steven H. Wright,
Pamela A. Knight, and
Elisabeth M. Thornton
From the Department of Veterinary Clinical Studies, Royal (Dick)
School of Veterinary Studies, The University of Edinburgh, Easter Bush
Veterinary Centre, Easter Bush, Roslin, Midlothian, Scotland.
Intestinal mucosal mast cells (IMMC) express granule neutral
proteases that are regulated by T-cell-derived cytokines, including interleukin-3 (IL-3) and IL-9, and by stem cell factor (SCF). The
IMMC-specific chymase, mouse mast cell protease-1 (mMCP-1), is released
in substantial quantities into the blood stream during gastrointestinal
allergic responses. We used cultured bone marrow-derived mast cells
(mBMMC) to identify cytokines that regulate the expression and
extracellular release of mMCP-1. When grown in IL-3-rich WEHI (15%
vol/vol) and 50 ng/mL recombinant rat SCF (rrSCF) bone marrow cells
supplemented with IL-9 (5 ng/mL) differentiated into mBMMC that
expressed a maximum of less than 250 ng mMCP-1/106 cells
and 189 ng mMCP-1/mL of culture supernatant. Supplementation of the
same three cytokines with transforming growth factor- 1 (TGF-1; 1 ng/mL) resulted in substantially enhanced
expression (6 µg/106 mBMMC) and extracellular release (2 µg/mL of culture supernatant) of mMCP-1. The response to
TGF-1 was dose-dependent, with maximal effect at 1 ng/mL, and was associated with immunohistochemical and ultrastructural
changes in the secretory granules. IL-9-induced expression of mMCP-1
may be due to endogenously expressed TGF-1, because it
was blocked by anti-TGF- antibodies. In conclusion, the expression
and extracellular release of the IMMC-specific chymase, mMCP-1, is
strictly regulated by TGF-1.
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