First Author | Garcia-Faroldi G | Year | 2013 |
Journal | J Immunol | Volume | 191 |
Issue | 3 | Pages | 1445-52 |
PubMed ID | 23817418 | Mgi Jnum | J:205716 |
Mgi Id | MGI:5546287 | Doi | 10.4049/jimmunol.1300216 |
Citation | Garcia-Faroldi G, et al. (2013) Active caspase-3 is stored within secretory compartments of viable mast cells. J Immunol 191(3):1445-52 |
abstractText | Caspase-3 is a main executioner of apoptotic cell death. The general notion is that, in viable cells, caspase-3 is found as a cytosolic inactive proenzyme and that caspase-3 activation is largely confined to processes associated with cell death. In this study, we challenge this notion by showing that enzymatically active caspase-3 is stored in viable mast cells. The enzymatically active caspase-3 was undetectable in the cytosol of viable cells, but was recovered in subcellular fractions containing secretory granule-localized proteases. Moreover, active caspase-3 was rapidly released into the cytosolic compartment after permeabilization of the secretory granules. Using a cell-permeable substrate for caspase-3, the presence of active caspase-3-like activity in granule-like compartments close to the plasma membrane was demonstrated. Moreover, it was shown that mast cell activation caused release of the caspase-3 to the cell exterior. During the course of mast cell differentiation from bone marrow cells, procaspase-3 was present in cells of all stages of maturation. In contrast, active caspase-3 was undetectable in bone marrow precursor cells, but increased progressively during the process of mast cell maturation, its accumulation coinciding with that of a mast cell-specific secretory granule marker, mouse mast cell protease 6. Together, the current study suggests that active caspase-3 can be stored within secretory compartments of viable mast cells. |