Molecular targets on mast cells and basophils for novel therapies
| Autor: | Ilkka T. Harvima, Marcus Maurer, Sheli Friedman, Ulrich Blank, Francesca Levi-Schaffer, Gunnar Nilsson, Bernhard F. Gibbs, Iva Polakovicova, Petr Dráber |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Immunology
Apoptosis Immunoglobulin E Cell Degranulation Ion Channels chemistry.chemical_compound Anti-Allergic Agents Hypersensitivity medicine Animals Humans Immunology and Allergy Bruton's tyrosine kinase Mast Cells Molecular Targeted Therapy Receptors Cannabinoid Receptor biology Receptors IgE Mast cell Basophils medicine.anatomical_structure chemistry Cancer research biology.protein Immunotherapy Prostaglandin D2 Immunoreceptor tyrosine-based inhibitory motif Cell Adhesion Molecules Tyrosine kinase Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Allergy and Clinical Immunology. 134:530-544 |
| ISSN: | 0091-6749 |
| DOI: | 10.1016/j.jaci.2014.03.007 |
| Popis: | Mast cells and basophils (MCs/Bs) play a crucial role in type I allergy, as well as in innate and adaptive immune responses. These cells mediate their actions through soluble mediators, some of which are targeted therapeutically by, for example, H1- and H2-antihistamines or cysteinyl leukotriene receptor antagonists. Recently, considerable progress has been made in developing new drugs that target additional MC/B mediators or receptors, such as serine proteinases, histamine 4-receptor, 5-lipoxygenase-activating protein, 15-lipoxygenase-1, prostaglandin D2, and proinflammatory cytokines. Mediator production can be abrogated by the use of inhibitors directed against key intracellular enzymes, some of which have been used in clinical trials (eg, inhibitors of spleen tyrosine kinase, phosphatidylinositol 3-kinase, Bruton tyrosine kinase, and the protein tyrosine kinase KIT). Reduced MC/B function can also be achieved by enhancing Src homology 2 domain-containing inositol 5' phosphatase 1 activity or by blocking sphingosine-1-phosphate. Therapeutic interventions in mast cell-associated diseases potentially include drugs that either block ion channels and adhesion molecules or antagonize antiapoptotic effects on B-cell lymphoma 2 family members. MCs/Bs express high-affinity IgE receptors, and blocking their interactions with IgE has been a prime goal in antiallergic therapy. Surface-activating receptors, such as CD48 and thymic stromal lymphopoietin receptors, as well as inhibitory receptors, such as CD300a, FcγRIIb, and endocannabinoid receptors, hold promising therapeutic possibilities based on preclinical studies. The inhibition of activating receptors might help prevent allergic reactions from developing, although most of the candidate drugs are not sufficiently cell specific. In this review recent advances in the development of novel therapeutics toward different molecules of MCs/Bs are presented. |
| Databáze: | OpenAIRE |
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