ABSTRACT
<p><b>OBJECTIVE</b>To determine the inhibitory effects of BIO-1211, a very late antigen-4 (vla-4) antagonist, on bronchoconstriction and neutrophil adhesion in rats.</p><p><b>METHODS</b>For evaluating ovalbumin-induced bronchoconstriction in the sensitized rats, the changes in lung resistance (RL) and lung dynamic compliance (C(dyn)) were determined after antigen challenge. Neutrophils from the rats were used to determine fibronectin and serum-induced cell adhesion. The effect of BIO-1211 on wheezing was determined after inhalation of histamine and acetylcholine in guinea pigs.</p><p><b>RESULT</b>BIO-1211 aerosol at 1, 3 and 10 mg/ml significantly inhibited the changes in lung resistance and lung dynamic compliance after antigen challenge in the sensitized rats in a dose-dependent manner. BIO-1211 at 25, 50, 100 and 200 microgram/ml inhibited the fibronectin-induced neutrophil adhesion by 23.5%, 24.6%, 61.4% and 58.1%, respectively, and serum-induced adhesion by 29.9%, 35.9%, 35.3% and 15.4%, respectively. Inhalation of 10 mg/ml BIO-1211 did not show any protection against histamine and acetylcholine-induced bronchoconstriction.</p><p><b>CONCLUSION</b>BIO-1211 inhibits bronchoconstriction and neutrophil adhesion, which may be associated with its effect against bronchoconstriction in rats.</p>
Subject(s)
Animals , Female , Male , Rats , Administration, Inhalation , Asthma , Drug Therapy , Bronchoconstriction , Physiology , Bronchodilator Agents , Pharmacology , Cell Adhesion , Guinea Pigs , Neutrophils , Cell Biology , Oligopeptides , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the immunoregulatory effects of pertussis protein on airway inflammatory, IFN-gamma/IL-4 ratio in bronchoalveolar lavage fluids(BALF) and airway hyperresponsiveness (AHR) in the sensitized mice.</p><p><b>METHODS</b>The sensitized mice were reexposed to ovalbumin and the airway response to methacholine injection was monitored. Inflammatory cells and cytokines IFN-gamma/IL-4 ratio in BALF were measured. Lung tissue specimens were collected for histological examination.</p><p><b>RESULT</b>Intramuscular injection or intranasal instillation of pertussis protein inhibited changes in lung resistance and lung dynamic compliance, upregulated IFN-gamma/IL-4 ratio and decreased eosinophil accumulation in a dose-dependent manner. Pathological examination showed that goblet cell hyperplasia and inflammatory cells infiltration in lung tissue were suppressed by pertussis protein.</p><p><b>CONCLUSION</b>Pertussis protein inhibits the inflammation and regulates the function of lungs in asthma mice, suggesting its potential application in treatment of asthma.</p>