Abstract
BackgroundMast cell secretory granules accommodate a large number of components, many of which interact with highly sulfated serglycin proteoglycan (PG) present within the granules. Polyamines (putrescine, spermidine and spermine) are absolutely required for the survival of the vast majority of living cells. Given the reported ability of polyamines to interact with PGs, we investigated the possibility that polyamines may be components of mast cell secretory granules.Methodology/Principal FindingsSpermidine was released by mouse bone marrow derived mast cells (BMMCs) after degranulation induced by IgE/anti-IgE or calcium ionophore A23187. Additionally, both spermidine and spermine were detected in isolated mouse mast cell granules. Further, depletion of polyamines by culturing BMMCs with α-difluoromethylornithine (DFMO) caused aberrant secretory granule ultrastructure, impaired histamine storage, reduced serotonin levels and increased β-hexosaminidase content. A proteomic approach revealed that DFMO-induced polyamine depletion caused an alteration in the levels of a number of proteins, many of which are connected either with the regulated exocytosis or with the endocytic system.Conclusions/SignificanceTaken together, our results show evidence that polyamines are present in mast cell secretory granules and, furthermore, indicate an essential role of these polycations during the biogenesis and homeostasis of these organelles.
Highlights
Mast cells participate both in the innate and adaptive immune response [1] and are thereby considered an important component of the immune system
Release of spermidine upon mast cell degranulation To address the possibility that polyamines are associated with mast cell secretory granules, we first investigated if polyamines are released upon mast cell degranulation
Polyamine depletion leads to altered ultrastructure of mast cell granules The previous results are compatible with the presence of polyamines in the mast cell granules, and we investigated whether a depletion of polyamines may provoke any alteration in the morphology/appearance of mast cell granules
Summary
Mast cells participate both in the innate and adaptive immune response [1] and are thereby considered an important component of the immune system. Among the inflammatory mediators released by mast cells, many are preformed and stored in secretory granules, and can be discharged upon exposure to a number of different stimuli such as crosslinking of IgE bound to the high affinity IgE receptor (FceRI) [8]. These mediators include biogenic amines such as histamine and serotonin, several mast cell-specific neutral proteases (mainly tryptases and chymases) and cytokines [9]. Mast cell secretory granules accommodate a large number of components, many of which interact with highly sulfated serglycin proteoglycan (PG) present within the granules. Given the reported ability of polyamines to interact with PGs, we investigated the possibility that polyamines may be components of mast cell secretory granules
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