Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Jan 2003
ReviewThe effect of anti-integrin monoclonal antibodies on antigen-induced pulmonary inflammation in allergic rabbits.
The integrin adhesion molecules are involved in the recruitment and activation of inflammatory cells at sites of inflammation in a variety of diseases. In the present study, we have investigated the effects of blocking monoclonal antibodies (mAbs) directed against CD49d (alpha(4) integrin), CD18 (beta(2) integrin) and the alpha sub-units of beta(2) integrin CD11a (LFA-1 integrin) and CD11b (Mac-1 integrin), on antigen (Ag)-induced acute bronchoconstriction and cellular recruitment in allergic rabbits in vivo. Inhaled Ag (Alternaria tenuis) challenge of neonatally sensitised rabbits caused an acute bronchoconstriction demonstrated by an increase in lung resistance (R(L)) and decrease in dynamic compliance (C(dyn)) and pulmonary inflammation characterised by an increase in bronchoalveolar lavage (BAL) inflammatory cells, particularly eosinophils, 24 h after challenge. ⋯ The data show that in the allergic rabbit model of asthma, VLA-4 (CD49d/CD29) only, is involved in the acute bronchoconstriction, suggesting an involvement of mast cell degranulation. Furthermore, eosinophil recruitment and activation appears to be mediated by a combination of VLA-4 (CD49d/CD29) and LFA-1 (CD18/CD11a). However in contrast, lymphocyte recruitment appears to be mediated by a combination of LFA-1 (CD18/CD11a) and Mac-1 (CD18/CD11b).
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Pulm Pharmacol Ther · Jan 2003
The use of surfactant in children with acute respiratory distress syndrome: efficacy in terms of oxygenation, ventilation and mortality.
The aim of this prospectively designed study was to investigate the efficacy of surfactant (S) for acute respiratory distress syndrome (ARDS) in children. ⋯ Modified natural surfactant is an effective treatment option in children with ARDS for improving gas exchange, decreasing the use of ventilatory support and increasing survival time.
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Pulm Pharmacol Ther · Jan 2003
Mechanisms of bronchopulmonary C-fiber hypersensitivity induced by cationic proteins.
Cationic proteins secreted by inflammatory cells infiltrating into the airways are known to cause mucosal injury and bronchial hyperresponsiveness. Although an involvement of bronchopulmonary C-fiber afferents in the cationic protein-induced airway hyperresponsiveness has been suggested, direct electrophysiological evidence has not been established. Accordingly, a series of studies was recently carried out using the single-fiber recording technique to determine the responses of pulmonary C fibers to cationic proteins and to investigate the mechanisms possibly underlying these effects. ⋯ Furthermore, the stimulatory and sensitizing effects of these proteins were completely nullified when their cationic charges were neutralized with negatively charged heparin before delivery. However, heparin administered 5-10 min after the delivery of cationic proteins was ineffective in reversing the effects. In conclusion, intratracheal instillation of cationic proteins consistently induces intense stimulation and sensitization of pulmonary C fibers, and an interaction between the cationic charges carried by these proteins and the airway mucosa is probably responsible.