Diverse exocytic pathways for mast cell mediators

Biochem Soc Trans. 2018 Apr 17;46(2):235-247. doi: 10.1042/BST20170450. Epub 2018 Feb 22.

Abstract

Mast cells play pivotal roles in innate and adaptive immunities but are also culprits in allergy, autoimmunity, and cardiovascular diseases. Mast cells respond to environmental changes by initiating regulated exocytosis/secretion of various biologically active compounds called mediators (e.g. proteases, amines, and cytokines). Many of these mediators are stored in granules/lysosomes and rely on intricate degranulation processes for release. Mast cell stabilizers (e.g. sodium cromoglicate), which prevent such degranulation processes, have therefore been clinically employed to treat asthma and allergic rhinitis. However, it has become increasingly clear that different mast cell diseases often involve multiple mediators that rely on overlapping but distinct mechanisms for release. This review illustrates existing evidence that highlights the diverse exocytic pathways in mast cells. We also discuss strategies to delineate these pathways so as to identify unique molecular components which could serve as new drug targets for more effective and specific treatments against mast cell-related diseases.

Keywords: Munc18; SNARE proteins; degranulation; exocytosis; mast cell; membrane fusion.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amines / metabolism
  • Animals
  • Cell Degranulation / drug effects
  • Cell Fusion
  • Cytokines / metabolism
  • Exocytosis*
  • Humans
  • Lysosomes / metabolism
  • Mast Cells / drug effects
  • Mast Cells / immunology*
  • Mast Cells / metabolism
  • Peptide Hydrolases / metabolism

Substances

  • Amines
  • Cytokines
  • Peptide Hydrolases