Comparison of inhibitory activities of zinc oxide ultrafine and fine particulates on IgE-induced mast cell activation

• Published in: Biometals 2009-12, Vol.22 (6), p.1031-1040
• Main Authors: Yamaki, Kouya, Yoshino, Shin
• Format: Article
• Language: English
• Subjects: Animals; beta-N-Acetylhexosaminidases - analysis; beta-N-Acetylhexosaminidases - secretion; Biochemistry; Biomedical and Life Sciences; Calcium - analysis; Cell Biology; Cell Degranulation - drug effects; Cell Degranulation - immunology; Cell Line; Cellular biology; Enzymes; Hypersensitivity - prevention & control; Immunoglobulin E - immunology; Immunoglobulin E - metabolism; Immunoglobulin E - pharmacology; Immunology; Life Sciences; Mast Cells - cytology; Mast Cells - drug effects; Mast Cells - immunology; Mast Cells - metabolism; Medicine/Public Health; Microbiology; Ovalbumin - immunology; Ovalbumin - pharmacology; Particle Size; Pharmacology/Toxicology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; Phosphorylation - immunology; Plant Physiology; Protein-Tyrosine Kinases - analysis; Protein-Tyrosine Kinases - metabolism; Proteins; Proto-Oncogene Proteins c-akt - analysis; Proto-Oncogene Proteins c-akt - metabolism; Rats; Receptors, IgE - immunology; Receptors, IgE - metabolism; Signal Transduction - drug effects; Signal Transduction - immunology; Tyrosine - metabolism; Zinc - analysis; Zinc Oxide - metabolism; Zinc Oxide - pharmacology; Zinc oxides
• ISSN: 0966-0844; 1572-8773
• DOI: 10.1007/s10534-009-9254-z

The effects of ultrafine and fine particles of zinc oxide (ZnO) on IgE-dependent mast cell activation were investigated. The rat mast cell line RBL2H3 sensitized with monoclonal anti-ovalbumin (OVA) IgE was challenged with OVA in the presence or absence of ZnO particles and zinc sulfate (ZnSO₄). Degranulation of RBL2H3 was examined by the release of β-hexosaminidase. To understand the mechanisms responsible for regulating mast cell functions, the effects of ZnO particles on the levels of intracellular Zn²⁺, Ca²⁺, phosphorylated-Akt, and global tyrosine phosphorylation were also measured. IgE-induced release of β-hexosaminidase was obviously attenuated by ultrafine ZnO particles and ZnSO₄, whereas it was very weakly inhibited by fine ZnO particles. The intracellular Zn²⁺ concentration was higher in the cells incubated with ultrafine ZnO particles than in those with fine ZnO particles. Consistent with inhibitory effect on release of β-hexosaminidase, ultrafine ZnO particles and ZnSO₄, but not fine ZnO particle, strongly attenuated the IgE-mediated increase of phosphorylated-Akt and tyrosine phosphorylations of 100 and 70 kDa proteins in RBL2H3 cells. These findings indicate that ultrafine ZnO particles, with a small diameter and a large total surface area/mass, could release Zn²⁺ easily and increase intracellular Zn²⁺ concentration efficiently, thus decreasing FcεRI-mediated mast cell degranulation through inhibitions of PI3K and protein tyrosine kinase activation. Exposure to ZnO particles might affect immune responses, especially in allergic diseases.