degranulation

Degranulation is the process by which certain cells release the contents of their secretory granules by fusing those granules with the plasma membrane, a form of regulated exocytosis. It is a key mechanism in immune and secretory systems, occurring in cells such as mast cells, basophils, neutrophils, eosinophils, cytotoxic T lymphocytes, and natural killer cells. It plays a role in host defense and tissue remodeling, but can also drive inflammation and allergic reactions when dysregulated.

Granules released by degranulation contain a variety of mediators tailored to the cell type. In mast cells and basophils, mediators include histamine, heparin, proteases (such as tryptase and chymase), and cytokines. In neutrophils and eosinophils, granules hold proteases, reactive oxygen species–generating enzymes, and cationic proteins such as elastase or major basic protein. Cytotoxic T lymphocytes and natural killer cells discharge lytic granules containing perforin and granzymes to kill target cells. The specific contents determine the local inflammatory, antimicrobial, or cytotoxic effects.

Mechanistically, degranulation is triggered by stimuli such as antigen–IgE interaction, complement components, cytokines, or microbial products, leading to calcium influx and the fusion of granule membranes with the plasma membrane via SNARE protein machinery. In cytotoxic lymphocytes, degranulation often occurs at the immunological synapse with a target cell, releasing cytotoxic molecules directly toward the target.

Clinical relevance includes allergic reactions and anaphylaxis driven by mast cell degranulation, as well as impaired degranulation contributing to certain immunodeficiencies. Methods to study degranulation include measuring mediator release, such as histamine or tryptase, from stimulated cells.