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-KitW/KitW-v [W/Wv]) mice to generate MC-reconstituted models. In asthma model experiments, no differences were observed in the symptoms of BL/6, W/Wv, BL/6-BMMC–reconstituted W/Wv, or hexb−/−-BMMC–reconstituted W/Wv mice. In Staphylococcus epidermidis experimental infection model experiments, the severity of symptoms and frequency of death were markedly higher in W/Wv and hexb−/−-BMMC–reconstituted W/Wv mice than in BL/6 and BL/6-BMMC–reconstituted W/Wv 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.

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

“…We hypothesize that the increased levels of these actin-associated proteins suggest actin remodeling enhances recruitment of immune cells and invasion of epithelial cells. Concurrent with this hypothesis, we observed a significant decrease in the lysosomal enzyme hexosaminidase B that plays a role in degradation of internalized Staphylococcus (106). Taken together, the regulatory systems described generate precise control of actin filament and network formation and participate in multiple aspects of pathogenesis (107)(108)(109)(110)(111)(112).…”

The role of myricetin fromRhodomyrtus tomentosa(Aiton) Hassk fruits on downregulation of FcɛRI‐mediated mast cell activation

“…The activation of mast cells causes the elevation of intracellular calcium, followed by the degranulation and the release of various pro‐inflammatory mediators (Galli & Tsai, ). Especially, β‐hexosaminidase is considered as a marker of mast cell degranulation and often used to screen anti‐allergic agents from natural products (Fukuishi et al, ). In this study, the suppressive effect of myricetin on mast degranulation was examined via measuring β‐hexosaminidase release from RBL‐2H3 cells.…”

Mast cells contribute to the induction of ocular mucosal alloimmunity

“…27 Corneal and conjunctival cell lysates analyzed by β-hexosaminidase assay demonstrated a significantly greater increase in β-hexosaminidase levels in graft recipients compared to naïve controls (P < .01; Figure 1B). 27 Corneal and conjunctival cell lysates analyzed by β-hexosaminidase assay demonstrated a significantly greater increase in β-hexosaminidase levels in graft recipients compared to naïve controls (P < .01; Figure 1B).…”