Comparison of inhibitory activities of zinc oxide ultrafine  and fine particulates on IgE-induced mast cell activation.
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 b-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 b-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 FceRI-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.
Yamaki
Kouya
K
Department of Pharmacology, Kobe Pharmaceutical University, 4-9-1 Motoyamakita-machi, Higashinada-ku, Kobe, Hyogo 658-8558, Japan. yam@kobepharma-u.ac.jp
Yoshino
Shin
S
D000818:Animals; D002118:Calcium / Q000032:analysis; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D006967:Hypersensitivity / Q000517:prevention & control; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010316:Particle Size; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism; D015032:Zinc / Q000032:analysis; D015034:Zinc Oxide / Q000378:metabolism / Q000494:pharmacology*; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis / Q000378:metabolism
D002118:Calcium; D007073:Immunoglobulin E; D010047:Ovalbumin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D017455:Receptors, IgE; D014443:Tyrosine; D015032:Zinc; D015034:Zinc Oxide; D001619:beta-N-Acetylhexosaminidases