Does ?-Hexosaminidase Function Only as a Degranulation Indicator in Mast Cells? The Primary Role of ?-Hexosaminidase in Mast Cell Granules.
J Immunol. 2014 Jul 11;
Authors: Fukuishi N, Murakami S, Ohno A, Yamanaka N, Matsui N, Fukutsuji K, Yamada S, Itoh K, Akagi M
Abstract
?-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 ?-hexosaminidase are present in the granules as opposed to the lysosome, and the biological role of MC ?-hexosaminidase has yet to be fully elucidated. Therefore, we investigated the biological role of ?-hexosaminidase in MC granules. Bone marrow-derived MCs from C57BL/6 (BL/6-BMMC) or ?-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 ?-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 ?-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 ?-hexosaminidase involves degradation of bacterial cell wall peptidoglycan.
PMID: 25015817 [PubMed – as supplied by publisher]
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