BACKGROUND: Mast cells are significantly involved in IgE-mediated allergic 
reactions; however, their roles in health and disease are incompletely 
understood.
OBJECTIVE: We aimed to define the proteome contained in mast cell releasates on 
activation to better understand the factors secreted by mast cells that are 
relevant to the contribution of mast cells in diseases.
METHODS: Bone marrow-derived cultured mast cells (BMCMCs) and peritoneal 
cell-derived mast cells were used as "surrogates" for mucosal and connective 
tissue mast cells, respectively, and their releasate proteomes were analyzed by 
mass spectrometry.
RESULTS: Our studies showed that BMCMCs and peritoneal cell-derived mast cells 
produced substantially different releasates following IgE-mediated activation. 
Moreover, we observed that the transglutaminase coagulation factor XIIIA 
(FXIIIA) was one of the most abundant proteins contained in the BMCMC 
releasates. Mast cell-deficient mice exhibited increased FXIIIA plasma and 
activity levels as well as reduced bleeding times, indicating that mast cells 
are more efficient in their ability to downregulate FXIIIA than in contributing 
to its amounts and functions in homeostatic conditions. We found that human 
chymase and mouse mast cell protease-4 (the mouse homologue of human chymase) 
had the ability to reduce FXIIIA levels and function via proteolytic 
degradation. Moreover, we found that chymase deficiency led to increased FXIIIA 
amounts and activity, as well as reduced bleeding times in homeostatic 
conditions and during sepsis.
CONCLUSIONS: Our study indicates that the mast cell protease content can shape 
its releasate proteome. Moreover, we found that chymase plays an important role 
in the regulation of FXIIIA via proteolytic degradation.