title: IgE-induced mast cell survival requires the prolonged generation of reactive oxygen species.
abstract: We show in this study that the ability of five different monomeric IgEs to enhance murine bone marrow-derived mast cell (BMMC) survival correlates with their ability to stimulate extracellular calcium (Ca(2+)) entry. However, whereas IgE+Ag more potently stimulates Ca(2+) entry, it does not enhance survival under our conditions. Exploring this further, we found that whereas all five monomeric IgEs stimulate a less robust Ca(2+) entry than IgE+Ag initially, they all trigger a more prolonged Ca(2+) influx, generation of reactive oxygen species (ROS), and ERK phosphorylation. These prolonged signaling events correlate with their survival-enhancing ability and positively feedback on each other to generate the prosurvival cytokine, IL-3. Interestingly, the prolonged ERK phosphorylation induced by IgE appears to be regulated by a MAPK phosphatase rather than MEK. IgE-induced ROS generation, unlike that triggered by IgE+Ag, is not mediated by 5-lipoxygenase. Moreover, ROS inhibitors, which block both IgE-induced ROS production and Ca(2+) influx, convert the prolonged ERK phosphorylation induced by IgE into the abbreviated phosphorylation pattern observed with IgE+Ag and prevent IL-3 generation. In support of the essential role that IgE-induced ROS plays in IgE-enhanced BMMC survival, we found the addition of H(2)O(2) to IgE+Ag-stimulated BMMCs leads to IL-3 secretion.
authors.affiliation: Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Sly
authors.forename: Janet
authors.initials: J
authors.lastname: Kalesnikoff
authors.forename: Vivian
authors.initials: V
authors.lastname: Lam
authors.forename: Dana
authors.initials: D
authors.lastname: Wong
authors.forename: Christine
authors.initials: C
authors.lastname: Song
authors.forename: Stephanie
authors.initials: S
authors.lastname: Omeis
authors.forename: Karen
authors.initials: K
authors.lastname: Chan
authors.forename: Corinna W K
authors.initials: CW
authors.lastname: Lee
authors.forename: Reuben P
authors.initials: RP
authors.lastname: Siraganian
authors.forename: Juan
authors.initials: J
authors.lastname: Rivera
authors.forename: Gerald
authors.initials: G
authors.lastname: Krystal