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Mast cell secretory granules: armed for battle

Subjects

Key Points

  • Mast cell secretory granules are lysosome-like organelles that contain a large panel of preformed bioactive constituents, including lysosomal hydrolases, amines, cytokines, proteases and proteoglycans.

  • Mast cell granule biogenesis is initiated in the trans-Golgi and is followed by extensive maturation processes, which are strongly dependent on proteoglycans of the serglycin type.

  • When mast cells are activated — for example, in the context of an allergic reaction — degranulation occurs, whereby the bioactive granule compounds are expelled to the cell exterior and can cause a powerful inflammatory reaction.

  • Mast cell degranulation is a highly complex process that involves a large number of kinases, adaptor molecules and second messengers, as well as extensive membrane fusion events, which are mediated by numerous factors.

  • Mast cells are implicated in many pathological conditions and their effects in such settings are often mediated by the compounds that are secreted from the mast cell granules.

  • Recent research has indicated that the mast cell-specific proteases — chymases, tryptases and carboxypeptidase A3 — account for many of the functions that are ascribed to mast cells.

Abstract

Mast cells are important effector cells of the immune system and recent studies show that they have immunomodulatory roles in diverse processes in both health and disease. Mast cells are distinguished by their high content of electron-dense secretory granules, which are filled with large amounts of preformed and pre-activated immunomodulatory compounds. When appropriately activated, mast cells undergo degranulation, a process by which these preformed granule compounds are rapidly released into the surroundings. In many cases, the effects that mast cells have on an immune response are closely associated with the biological actions of the granule compounds that they release, as exemplified by the recent studies showing that mast cell granule proteases account for many of the protective and detrimental effects of mast cells in various inflammatory settings. In this Review, we discuss the current knowledge of mast cell secretory granules.

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Figure 1: Mast cell granule morphology.
Figure 2: A highly simplified scheme for mast cell granule biogenesis, maturation and degranulation.
Figure 3: Biological effects of mast cell granule components.

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Acknowledgements

The authors are supported by grants from The Swedish Research Council (G.P. and S.W.), The Swedish Cancer Foundation (G.P.), The Swedish Heart and Lung Foundation (G.P.) and Formas, Sweden (G.P.).

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Glossary

Tryptases

Serine proteases that have trypsin-like cleavage specificities — that is, they cleave peptide bonds on the carboxy-terminal side of arginine or lysine residues.

Chymases

Serine proteases that have chymotrypsin-like cleavage specificities — that is, they cleave peptide bonds on the carboxy-terminal side of aromatic amino acid residues.

Beige mice

A strain of mice with beige hair and a mutation in the gene that encodes lysosomal trafficking regulator (Lyst). These mice have an autosomal recessive disorder that is characterized by hypopigmentation and immune cell dysfunction. The phenotype of beige mice results from aberrant lysosomal trafficking and is similar to that of patients with Chediak–Higashi syndrome.

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Wernersson, S., Pejler, G. Mast cell secretory granules: armed for battle. Nat Rev Immunol 14, 478–494 (2014). https://doi.org/10.1038/nri3690

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