Molecular Biology of Mast Cell Secretory Granule Proteoglycans and Proteases

Abstract

Mast cells and a large number of other hematopoietic cells have secretory granules which contain a unique family of proteoglycans. In the case of the roast cell, these proteoglycans are exocytosed when the IgE receptors on the cell’s plasma membrane are cross-linked with antigen (Yurt et al. 1977). While a number of functions haive been attributed to secretory granule proteoglycans of hematopoietic cells, it appears that a major function is to interact specifically with basically charged secretory granule proteins (Yurt and Austen 1977; Serafin et al. 1986). Mast cells have been found to contain large amounts of basically charged serine proteases that are enzymatically active at neutral pH (Woodbury et al. 1978; Schwartz et al. 1981; Dubuske et al. 1984; Shechter et al. 1986; LeTrong et al. 1987). In the rat serosal mast cell (Everitt and Neurath 1980), the mouse bone marrow-derived mast cell (BMMC) (Serafin et al. 1987), and the human skin mast cell (Goldstein et al. 1987)], the proteoglycans and serine proteases have been shown to be also packaged with basically charged carboxypeptidases. These endopeptidases and exopeptidases are stored in active form in secretory granules, and therefore it is likely that one of the functions of proteoglycans in mast cells is to package the enzymes in a configuration that minimizes their autolysis. When the composition of the protease/proteoglycan macromolecular complex in the mouse BMMC was examined during the stage of differentiation in which the cell was synthesizing both chondroitin sulfate E proteoglycan and heparin proteoglycan, it was discovered that the macromolecular complex was preferentially enriched for heparin proteoglycans (Serafin et al. 1986). In addition, when different Kirsten sarcoma virus immortalized mast cell (KiSV-MC) lines were examined for their protease activities and biosynthesis of proteoglycans, a strong positive correlation was observed in carboxypeptidase A content and biosynthesis of heparin proteoglycans relative to chondroitin sulfate E proteoglycans (Reynolds et al. 1988). Thus for proteoglycans, the type of the glycosaminoglycan that is polymerized onto the serine/glycine-rich peptide core may be related to the type of protein with which the proteoglycan is to interact inside the secretory granule.