Does β-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of β-Hexosaminidase in Mast Cell Granules

beta-Hexosaminidase, which is generally present in the lysosome, is essential for glycoprotein metabolism in the maintenance of cell homeostasis. In mast cells (MCs), large amounts of beta-hexosaminidase are present in the granules as opposed to the lysosome, and the biological role of MC beta-hexosaminidase has yet to be fully elucidated. Therefore, we investigated the biological role of beta-hexosaminidase in MC granules. Bone marrow-derived MCs from C57BL/6 (BL/6-BMMC) or beta-hexosaminidase gene-deficient (hexb(-/-) -BMMC) mice were transplanted into MC-deficient (WBB6F1/J-Kit(W) /Kit(W-v) [W/W-v]) mice to generate MC-reconstituted models. In asthma model experiments, no differences were observed in the symptoms of BL/6, W/W-v, BL/6-BMMC-reconstituted W/W-v, or hexb(-/-) -BMMC-reconstituted W/W-v mice. In Staphylococcus epidermidis experimental infection model experiments, the severity of symptoms and frequency of death were markedly higher in W/W-v and hexb(-/-) -BMMC-reconstituted W/W-v mice than in BL/6 and BL/6-BMMC-reconstituted W/W-v mice. The growth of S. epidermidis in an in vitro study was clearly inhibited by addition of BL/6-BMMC lysate, but not by addition of hexb(-/-)-BMMC lysate. Moreover, suppression of bacterial proliferation was completely recovered when bacteria were incubated with hexb(-/-)-BMMC lysate plus beta-hexosaminidase. Transmission electron microscopy indicated that the cell wall of S. epidermidis was heavily degraded following coincubation of bacteria with BL/6-BMMC lysate, but not following coincubation with hexb(-/-)-BMMC lysate. These findings strongly suggest that MC granule beta-hexosaminidase is crucial for defense against bacterial invasion, but is not involved in the allergic response. Our results also suggest that the bactericidal mechanism of beta-hexosaminidase involves degradation of bacterial cell wall peptidoglycan.