Dipeptidyl peptidase I is essential for activation of mast cell chymases, but not tryptases, in mice.
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 -/- 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.
Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, California 94143-0911, USA. pjwolt@itsa.ucsf.edu
P J
PJ
Wolters
C T
CT
Pham
D J
DJ
Muilenburg
T J
TJ
Ley
G H
GH
Caughey
D000818:Animals; D020789:Cathepsin C / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D053818:Chymases; D004789:Enzyme Activation / Q000235:genetics; D017353:Gene Deletion; D015971:Gene Expression Regulation, Enzymologic; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D053802:Tryptases
C509190:Tpsb2 protein, mouse; D020789:Cathepsin C; D012697:Serine Endopeptidases; D053818:Chymases; C509222:Tpsab1 protein, mouse; D053802:Tryptases