Granule maturation in mast cells: histamine in control.

Mast cells are derived from committed progenitors that originate in the BM. They mature into histochemically distinguishable, metachromatic mast cells containing numerous cytoplasmic secretory granules. Accumulating evidence demonstrates that mast cell granule maturation is very tightly regulated by many factors including different granule components such as proteoglycans. In this issue of the European Journal of Immunology, Nakazawa et al. [Eur. J. Immunol. 2014. 44: 204-214] highlight a role for mast cell derived histamine as another factor critical for mast cell maturation. Using histidine decarboxylase (HDC) deficient mice that are unable to make histamine, they show poorly formed secretory granules and decreased secretory granule protease expression in peritoneal mast cells. Co-culturing BM-derived mast cells with fibroblasts normally drives granule maturation, but HDC-deficient BM-derived mast cells fail to do so. Exogenously provided histamine partly restores granule differentiation as evidenced by increased tryptase and chymase activity, and this is histamine receptor type H4 -dependent. However, H4 -deficient mice have intact granule formation in peritoneal mast cells, suggesting that when HDC is functional, the intrinsic histamine production is sufficient for most granule maturation processes and H4 is dispensable. This study highlights the role of histamine in the regulation of mast cell maturation, although the cytosolic target remains unknown.