The Role of Actin Microfilaments in the Down-Regulation of the Degranulation Response in RBL-2H3 Mast Cells

摘要: Cross-linking of FceRI on rat basophilic leukemia (RBL) cells initiates a signaling cascade leading to degranulation the and release inflammatory mediators. Inhibitors that disrupt microfilaments, such as latrunculin cytochalasin D, do not cause any their own, but they enhance FceRI-mediated degranulation. Dose-response studies show good correlation between inhibition actin polymerization increased In RBL cells, causes decrease in basal levels filamentous (F-actin), while D does not. This is particularly evident Triton-insoluble pool F-actin which highly cross-linked associated with plasma membrane. A concentration 500 nM decreases level by 60–70% total 25%. Latrunculin increases both rate extent Ag-induced having no effect pervanadate-induced Pervanadate activates pathways directly bypasses cross-linking receptor. activated through presence latrunculin, phospholipase activity well tyrosine phosphorylation Syk receptor itself kinase Lyn. indicates very earliest events after are enhanced. These results suggest microfilaments may interact, either or indirectly, regulate process at phosphorylation. Microfilaments possibly act uncoupling Lyn from