Transient fusion ensures granule replenishment to maintain repeated release after IgE-mediated mast cell degranulation

Abstract

To ensure normal immune function, mast cells (MC) employ different pathways to release mediators. Here, we report a thus far unknown capacity of MC to recycle and reuse secretory granules (SG) after an antigen-evoked degranulation process under physiological conditions; this phenomenon involves the existence of a recycling SG pool available for release in a short time-scale. Approximately 60% of the total recycled SG was promoted by rapid endocytic modes, which involved kiss-and-run and cavicapture mechanisms, causing retention of the intragranular matrix. We found the presence of normal-size granules and giant actomyosin- and dynamin-dependent granules, which were characterized by large quantal content. These large structures allowed the recovered MC to release a large amount of 5-HT, compensating for the decrease in the number of exocytosed SG. This work uncovers a new physiological role of the exo-endocytosis cycle in the immunological plasticity of MC and reveals a novel property of their biological secretion.