Mast cells are central effector cells in @entity56 and are augmented in the airways of @entity565 @entity1 . Attenuating mast cell degranulation and with it the early asthmatic response is an important intervention point to inhibit bronchoconstriction, plasma exudation and tissue @entity4 formation. To validate the efficacy of novel pharmacological interventions, appropriate and practicable in vivo models reflecting mast cell-dependent mechanisms in the lung, are missing. Thus, we developed a novel model of passive @entity358 in @entity35 . @entity35 were passively sensitized by concurrent intratracheal and intradermal (ear) application of an anti-DNP IgE antibody. Intravenous application of the antigen, DNP-BSA in combination with @entity23045 dye, led to mast cell degranulation in both tissues. Quantification of mast cell degranulation in the lung was determined by (1) mediator release into bronchoalveolar lavage, (2) extravasation of Evans blue dye into tracheal and bronchial lung tissue and (3) invasive measurement of antigen-induced bronchoconstriction. Quantification of mast cell degranulation in the ear was determined by extravasation of Evans blue dye into ear tissue. We pharmacologically validated our model using the SYK inhibitor @entity30210 , the H1-receptor antagonist @entity14295 , the mast cell stabilizer @entity9992 (DSCG) and the b2-adrenergic receptor agonist @entity6410 . @entity30210 was equally efficacious in lung and ear. @entity14295 effectively inhibited bronchoconstriction and ear vascular leakage, but was less effective against @entity358 , perhaps reflecting the differing roles for @entity112 receptor sub-types. DSCG attenuated both vascular leakage in the lung and bronchoconstriction, but with a very short duration of action. As an inhaled approach, @entity6410 was more effective in the lung than in the ear. This model of passive @entity358 provides a tissue relevant readout of early mast cell activity and pharmacological benchmarking broadly reflects responses observed in @entity1 with @entity565 .

A Novel Model of IgE-Mediated Passive Pulmonary Anaphylaxis in XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity565 :: ('MESH:D001249', 'Disease') :: ['asthma'] @entity4 :: ('MESH:D004487', 'Disease') :: ['oedema'] @entity23045 :: ('MESH:D005070', 'Chemical') :: ['Evans blue'] @entity112 :: ('MESH:D006632', 'Chemical') :: ['histamine'] @entity30210 :: ('MESH:C523665', 'Chemical') :: ['Fostamatinib'] @entity358 :: ('MESH:D008171', 'Disease') :: ['pulmonary vascular leakage', 'pulmonary anaphylaxis'] @entity56 :: ('MESH:D004342', 'Disease') :: ['allergic asthma'] @entity9992 :: ('MESH:D004205', 'Chemical') :: ['disodium cromoglycate'] @entity35 :: ('10116', 'Species') :: ['Rats', 'rats'] @entity6410 :: ('MESH:C012629', 'Chemical') :: ['Formoterol'] @entity14295 :: ('MESH:C121345', 'Chemical') :: ['Desloratadine']
@entity35 :: (10116,Species) :: ['Rats']
