By Novartis Foundation(eds.)
The publication offers fresh advances in relation to the standards and mechanisms that control the expansion, differentiation and serve as of mast cells and basophils; dialogue of latest applied sciences used to check those cells, and integration of the fundamental clinical findings within the context of healing chances for the remedy of ailments comparable to allergic irritation and autoimmune ailment that are mediated, partially, via those granulocytes.Content:
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Additional info for Mast Cells and Basophils: Development, Activation and Roles in Allergic/Autoimmune Disease: Novartis Foundation Symposium 271
IgE half-life in the mouse is so short we have tried injecting the IgE very shortly before the sensitization. We haven’t tried more prolonged experiments. It was the day before we did the experiment. Metcalfe: Does the IgE have to be added systemically? There is trafficking going on. I am curious as to whether the cells in the skin that are already there can simply be turned on by adding IgE locally, or whether or not there is a more general phenomenon. Oettgen: We have only done it that way. We have avoided the intradermal injection for fear that injection would elicit a cytokine response in terms of injury that would obscure the result.
Remarkably, although this IgE effect is mediated via FceRI and mast cells, it does not require exposure to antigens for which the IgE has known specificity. We hypothesize that a potential mechanism whereby IgE can support optimal immune sensitization involves the maintenance of a cutaneous cytokine milieu favourable to dendritic cell activation and T cell sensitization (Fig. 5). Acknowledgements HCO is supported by NIH/NIAID 1-R01-AI054471 and SJG and MT are supported by NIH R01-CA72074, R37-AI23990 and P01-HL67674 (Project 2).
Amplification of signalling by Fyn and Lyn The events following Lyn-dependent phosphorylation of FceRI are well characterized and reviewed in detail (Kinet 1999). Briefly, Lyn is required for full activation of Syk kinase because phosphorylation of FceRI creates the phospho-ITAMs required for Syk interaction and activation. Syk phosphorylates multiple proteins but one key molecule that is a target of Syk activity is the linker for activation of T cells (LAT), which scaffolds a macromolecular signalling complex that includes proteins like PLCg, SLP-76 and Vav1 (Zhang et al 1998, Saitoh et al 2000, Saitoh et al 2003).