Exposure of RBL-2H3 mast cells to Ag(+) induces cell degranulation and mediator release.
There is a growing need to understand the impact of environmental sulfhydryl group-reactive heavy metals on the immune system. Here we show that Ag(+) induces mast cell degranulation, as does the aggregation of the high affinity immunoglobulin E receptor (FcepsilonRI). Micromolar quantities of Ag(+) specifically induced degranulation of mast cell model rat basophilic leukemia (RBL-2H3) cells without showing cytotoxicity. The Ag(+)-mediated degranulation could be observed as rapidly as 5 min after the addition of the ions. Ag(+) also induced a rapid change in tyrosine phosphorylation of multiple cellular proteins including the focal adhesion kinase but not Syk kinase. The Syk-selective inhibitor piceatannol and the Src family-selective tyrosine kinase inhibitor PP1 dose-dependently inhibited FcepsilonRI-mediated degranulation, whereas neither compound inhibited the Ag(+)-mediated degranulation. Furthermore, likewise FcepsilonRI aggregation, Ag(+) also induced leukotriene secretion. These results show that Ag(+) activates RBL-2H3 mast cells through a tyrosine phosphorylation-linked mechanism, which is distinct from that involved in FcepsilonRI-mediated activation.
Suzuki
Y
Y
Department of Immunology and Microbiology, Nihon University School of Medicine, Tokyo, 173-8610, Japan. ysuzuki@med.nihon-u.ac.jp
Yoshimaru
T
T
Yamashita
K
K
Matsui
T
T
Yamaki
M
M
Shimizu
K
K
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006636:Histamine Release / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins; D015289:Leukotrienes / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D008628:Mercury / Q000633:toxicity; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism; D012834:Silver / Q000633:toxicity*; D000072377:Syk Kinase; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D015289:Leukotrienes; D011506:Proteins; D017455:Receptors, IgE; D012834:Silver; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D000072377:Syk Kinase; C000606898:Syk protein, rat; D008628:Mercury