title: Does β-hexosaminidase function only as a degranulation indicator in mast cells? The primary role of β-hexosaminidase in mast cell granules.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Tokushima 770-8514, Japan; nobuf@ph.bunri-u.ac.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukuishi
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Tokushima 770-8514, Japan;
authors.forename: Shinya
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Tokushima 770-8514, Japan;
authors.forename: Akane
authors.initials: A
authors.lastname: Ohno
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Tokushima 770-8514, Japan;
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamanaka
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Tokushima 770-8514, Japan;
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Matsui
authors.affiliation: Department of Microbiology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan; and.
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukutsuji
authors.affiliation: Department of Microbiology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan; and.
authors.forename: Sakuo
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Department of Medicinal Biotechnology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Tokushima 770-8503, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Tokushima 770-8514, Japan;
authors.forename: Masaaki
authors.initials: M
authors.lastname: Akagi
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology; D015550:Cell Degranulation; D002473:Cell Wall / Q000276:immunology; D003594:Cytoplasmic Granules / Q000201:enzymology*; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010457:Peptidoglycan / Q000276:immunology / Q000378:metabolism; D013203:Staphylococcal Infections / Q000276:immunology* / Q000401:mortality; D013212:Staphylococcus epidermidis / Q000276:immunology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D010457:Peptidoglycan; D001619:beta-N-Acetylhexosaminidases