Activin and transforming growth factor-beta signaling pathways are activated after allergen challenge in mild asthma.

Background: Both transforming growth factor (TGF)-beta(1) and activin-A have been implicated in airway remodeling in asthma, but the modulation of their specific signaling pathways after disease activation remains undefined.

Objective: To define the expression kinetics of TGF-beta(1), activin-A ligands, and follistatin (a natural activin inhibitor), their type I and type II receptors (activin-like kinase[ALK]-1, ALK-5, ALK-4, TbetaRII, and ActRIIA/RIIB) and activation of signaling (via phosphorylated (p) Smad2), in the asthmatic airway after allergen challenge.

Methods: Immunohistochemistry was performed on bronchial biopsies from 15 mild atopic patients with asthma (median age, 25 years; median FEV(1)% predicted, 97%) at baseline and 24 hours after allergen inhalation.

Basal expression of bone morphogenetic protein receptor is reduced in mild asthma.

Rationale: Despite increasing recognition of bone morphogenetic protein (BMP) signaling in tissue remodeling, the expression pattern of ligands and signaling pathways remain undefined in the asthmatic airway.

Objectives: To determine expression of BMP ligands (BMP-2, BMP-4, and BMP-7) and type I and type II receptors (ALK-2, ALK-3, ALK-6, and BMPRII) as well as evidence for activation of BMP signaling via detection of phosphorylated Smad1/5 (pSmad1/5) expression in asthmatic airways at baseline (compared with nonasthmatic controls), and after allergen challenge.

Methods: Bronchial biopsies were obtained from 6 nonasthmatic control volunteers, and 15 atopic patients with asthma (median age, 25 yr; median FEV(1)% predicted, 97%) at baseline, then at 24 hours and 7 days after allergen challenge.

Skin reactivity and local cell recruitment in human atopic and nonatopic subjects by CCL2/MCP-1 and CCL3/MIP-1alpha.

Background: Monocyte chemotactic protein (MCP-1/CCL2), the ligand for CCR2 and CCR5, and macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3), the ligand for CCR1 and CCR5, are potent chemo-attractants in vitro and produce lesions in experimental animals, which resemble immediate and delayed-type hypersensitivity (DTH) reactions. CCL3 induces mononuclear cell and granulocyte infiltration in human atopic and nonatopic skin. Whether CCL2 (MCP-1) has comparable activity in man is uncertain as is the capacity of both the chemokines to elicit immediate- and DTH-like reactions in humans.

Remodeling and airway hyperresponsiveness but not cellular inflammation persist after allergen challenge in asthma.

Rationale: Airway hyperresponsiveness (AHR) increases up to 2 weeks after allergen inhalational challenge of subjects with asthma who show a late-phase asthmatic reaction (dual responders). Cellular inflammation and airway remodeling are increased 24 hours after allergen challenge.

Objectives: To determine whether persistence of increased AHR is associated with persistent activation of remodeling and enhanced inflammation.