Inhibition of Spleen Tyrosine Kinase Prevents Mast Cell Activation and Airway Hyperresponsiveness

• DOI: 10.1164/rccm.200503-361oc
• Publication Date: 2005-09-29T00:34:12Z
• Authors: Shigeki Matsubara; Guiming Li; Katsuyuki Takeda; Joan E. Loader; Polly Pine; Esteban S. Masuda; Nobuaki Miyahara; Satoko Miyahara; Joseph J. Lucas; Azzeddine Dakhama; Erwin W. Gelfand
• Keywords: Airway hyperresponsiveness

Spleen tyrosine kinase (Syk) is important for Fc and B-cell receptor-mediated signaling.To determine the activity of a specific Syk inhibitor (R406) on mast cell activation in vitro development allergen-induced airway hyperresponsiveness (AHR) inflammation vivo.AHR were induced after 10 d allergen (ovalbumin [OVA]) exposure exclusively via airways absence adjuvant. This approach was previously established to be IgE, FcepsilonRI, dependent. Alternatively, mice passively sensitized with OVA-specific followed by limited challenge. In vitro, added cultures IgE-sensitized bone marrow-derived cells (BMMCs) before cross-linking allergen.The prevented OVA-induced degranulation murine BMMCs inhibited production interleukin (IL)-13, tumor necrosis factor alpha, IL-2, IL-6 these BMMCs. When administered vivo, R406 AHR, which developed BALB/c exposed aerosolized 1% OVA consecutive (20 min/d), as well pulmonary eosinophilia goblet metaplasia. A similar inhibition AHR demonstrated IgE challenge.This study delineates functional role cell- IgE-mediated inflammation, results indicate that may target treatment allergic asthma.