First Author | Fukuishi N | Year | 2014 |
Journal | J Immunol | Volume | 193 |
Issue | 4 | Pages | 1886-94 |
PubMed ID | 25015817 | Mgi Jnum | J:317584 |
Mgi Id | MGI:6843910 | Doi | 10.4049/jimmunol.1302520 |
Citation | Fukuishi N, et al. (2014) Does beta-hexosaminidase function only as a degranulation indicator in mast cells? The primary role of beta-hexosaminidase in mast cell granules. J Immunol 193(4):1886-94 |
abstractText | 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. |