Does β-hexosaminidase function only as a degranulation indicator in mast cells? The primary role of β-hexosaminidase in mast cell granules

• Published in: The Journal of immunology (1950) Vol. 193; no. 4; pp. 1886 - 1894
• Main Authors: Fukuishi, Nobuyuki, Murakami, Shinya, Ohno, Akane, Yamanaka, Naoya, Matsui, Nobuaki, Fukutsuji, Kenji, Yamada, Sakuo, Itoh, Kouji, Akagi, Masaaki
• Format: Journal Article
• Language: English
• Published: United States 15.08.2014
• Subjects: Animals; Asthma - immunology; beta-N-Acetylhexosaminidases - metabolism; Cell Degranulation; Cell Wall - immunology; Cytoplasmic Granules - enzymology; Disease Models, Animal; Glycoproteins - metabolism; Lysosomes - enzymology; Mast Cells - enzymology; Mast Cells - immunology; Mast Cells - transplantation; Mice; Mice, Inbred C57BL; Mice, Knockout; Peptidoglycan - immunology; Peptidoglycan - metabolism; Staphylococcal Infections - immunology; Staphylococcal Infections - mortality; Staphylococcus epidermidis; Staphylococcus epidermidis - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1302520

β-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 β-hexosaminidase are present in the granules as opposed to the lysosome, and the biological role of MC β-hexosaminidase has yet to be fully elucidated. Therefore, we investigated the biological role of β-hexosaminidase in MC granules. Bone marrow-derived MCs from C57BL/6 (BL/6-BMMC) or β-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 β-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 β-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 β-hexosaminidase involves degradation of bacterial cell wall peptidoglycan.