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J. Biol. Chem., Vol. 276, Issue 21, 18551-18556, May 25, 2001
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From the Dipeptidyl peptidase I (DPPI) is the sole
activator in vivo of several granule-associated serine
proteases of cytotoxic lymphocytes. In vitro, DPPI also
activates mast cell chymases and tryptases. To determine whether DPPI
is essential for their activation in vivo, we used enzyme
histochemical and immunohistochemical approaches and solution-based
activity assays to study these enzymes in tissues and bone
marrow-derived mast cells (BMMCs) from DPPI +/+ and DPPI
Dipeptidyl Peptidase I Is Essential for Activation of Mast Cell
Chymases, but Not Tryptases, in Mice*
§,
,,
Department of Medicine and Cardiovascular
Research Institute, University of California, San Francisco, California
94143-0911 and the ¶ Departments of Internal Medicine,
Pathology and Immunology, and ** Genetics, Washington University
School of Medicine, St. Louis, Missouri 63110-1093
/ mice. We
find that DPPI / mast cells contain normal amounts of
immunoreactive chymases but no chymase activity, indicating that DPPI
is essential for chymase activation and suggesting that DPPI / mice
are functional chymase knockouts. The absence of DPPI and chymase
activity does not affect the growth, granularity, or staining
characteristics of BMMCs and, despite prior predictions, does not alter
IgE-mediated exocytosis of histamine. In contrast, the level of active
tryptase (mMCP-6) in DPPI / BMMCs is 25% that of DPPI +/ BMMCs.
These findings indicate that DPPI is not essential for mMCP-6
activation but does influence the total amount of active mMCP-6 in mast
cells and therefore may be an important, but not exclusive mechanism
for tryptase activation.
*
This work was supported in part by the American Lung
Association of California and National Institutes of Health Grants
HL-04055 (to P. J. W.), HL-03774 (to C. T. N. P.), DK-49786 (to
T. J. L.), and HL-24136 (to G. H. C.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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