Serine proteinases are regionally segregated within mast cell granules

By ultrastructure, human skin mast cell granules exhibit amorphous regions situated next to crystalline regions with scroll, lamellar, and grating/lattice-like configurations. The composition and function of these structural domains is unknown. These granules also contain large amounts of three serine proteinases termed tryptase, chymase, and cathepsin G. In this study, subgranular proteinase distribution is correlated with granule ultrastructure.

Human skin sections were immunolabeled for each proteinase, visualized with gold-conjugated antibodies, and then stained with heavy metals to enhance granule features. Both single and double labeling experiments were analyzed.

Comparison of the immunogold labeling patterns revealed nonrandom distributions for each proteinase within most granules. At low magnification, chymase and cathepsin G immunoreactivity was found preferentially over more electron-dense granule subregions, whereas tryptase immunoreactivity was found preferentially over less electron-dense subregions. The complimentary staining pattern of the proteinases was also observed in double labeling experiments where tryptase immunoreactivity was compared directly with that of chymase or cathepsin G. Higher magnification of sections revealed that electron-dense granule areas corresponded to amorphous regions, whereas less dense regions most often demonstrated crystalline structures.

These observations correlate the subgranular distribution of serine proteinases with specific granule ultrastructure and suggest that the different morphologic features within granules may be related, in part, to the packaging of serine proteinases. Human mast cells differ from human basophils and rat mast cells by virtue of the presence of high amounts of tryptase and the presence of crystalline substructures. This raises the possibility that association of tryptase with crystalline structures reflects a specialized form of packaging permitting efficient storage of high levels of this proteinase within mast cell granules.