Molecular targets on mast cells and basophils for novel therapies

0435403 - ÚMG 2015 RIV US eng J - Článek v odborném periodiku
Harvima, I.T. - Levi-Schaffer, F. - Dráber, Petr - Friedman, S. - Polakovičová, Iva - Gibbs, B.F. - Blank, U. - Nilsson, G. - Maurer, M.
Molecular targets on mast cells and basophils for novel therapies.
Journal of Allergy and Clinical Immunology. Roč. 134, č. 3 (2014), s. 530-544. ISSN 0091-6749. E-ISSN 1097-6825
Grant CEP: GA MŠMT LD12073; GA ČR(CZ) GBP302/12/G101; GA ČR(CZ) GA14-09807S; GA ČR(CZ) GA14-00703S
Institucionální podpora: RVO:68378050
Klíčová slova: cell activation * mast cells and basophils * treatment of allergic diseases
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 11.476, rok: 2014

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 D-2, 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, Fc gamma RIIb, 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.
Trvalý link: http://hdl.handle.net/11104/0239550