Molecular targets on mast cells and basophils for novel therapies

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Presentation transcript:

Molecular targets on mast cells and basophils for novel therapies Ilkka T. Harvima, MD, PhD, Francesca Levi-Schaffer, PharmD, PhD, Petr Draber, PhD, Sheli Friedman, MSc, Iva Polakovicova, MSc, Bernhard F. Gibbs, PhD, Ulrich Blank, PhD, Gunnar Nilsson, PhD, Marcus Maurer, MD Journal of Allergy and Clinical Immunology Volume 134, Issue 3, Pages 530-544 (September 2014) DOI: 10.1016/j.jaci.2014.03.007 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Soluble mediators of MCs, Bs, or both as targets for novel therapy. The effects of mediators stored in the secretory granules or produced de novo on cell activation can be prevented by drugs targeting tryptase, chymase, and/or cathepsin G by drugs targeting 5-LO, FLAP, 15-LO-1 or prostaglandin D synthase (PGDS); by mAbs targeting proinflammatory cytokines; or by specific receptor antagonists. TP, Thromboxane receptor. Journal of Allergy and Clinical Immunology 2014 134, 530-544DOI: (10.1016/j.jaci.2014.03.007) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Intracellular signaling pathways of MCs, Bs, or both as targets for novel therapy. Antigen-aggregated IgE-FcεRI complexes or stem cell factor (SCF)–activated KIT initiate signaling pathways leading to degranulation, chemotaxis, and/or apoptosis depending on the signaling pathway triggered. Some of the proteins and other effectors executing these processes (in yellow and blue boxes) can be inhibited or potentiated by various drugs (in red), as described in the text. Aa BCL-2 FM, Antiapoptotic BCL-2 family members; ER, endoplasmic reticulum; IP3, inositol triphosphate; IP3R, inositol triphosphate receptor; PKC, protein kinase C; PLC, phospholipase C; PM, plasma membrane. Journal of Allergy and Clinical Immunology 2014 134, 530-544DOI: (10.1016/j.jaci.2014.03.007) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Novel surface receptors that alter IgE-dependent mediator release in MCs, Bs, or both. Stimulation of inhibitory receptors, such as CB1, CD300a, FcγRIIB, and Siglec-8, or blockade of surface activating receptors, such as CD48 and TSLPR, could potentially serve as targets for future allergy therapy. PEA, Palmitoylethanolamide. Journal of Allergy and Clinical Immunology 2014 134, 530-544DOI: (10.1016/j.jaci.2014.03.007) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions