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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The mucus lining of the respiratory tract originates from products of secretory cells interspersed among mucosal cells or within submucosal glands and protects the underlying mucosa from dehydration. Current understanding is that the lining is a two-fluid model in which the upper layer is a viscoelastic gel (mucus, cross-linked glycoproteins) that overlies a sol layer (serous). Thus mucus propelled by ciliary beating, flows above the sol layer and contains sloughed cells and xenobiotic materials that come into contact with it. ⋯ If high velocity of expiratory airflow is preserved then even with chronic exposure to respiratory irritants and cigarette smoke, mucus clearance remains effective due to cough and two-phase, gas-liquid interactions. However, in patients with advanced airway obstruction and incapable of generating forceful expiratory flows, cough and shearing are ineffective and mucociliary clearance is disparate with markedly slowed mucus layer transport within central airways. Mucolytic therapy for patients with advanced airway obstruction improves ventilation and reduces the frequency of exacerbation.
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Pulm Pharmacol Ther · Jan 2002
ReviewDelta-opioid receptor antagonists as a new concept for central acting antitussive drugs.
Our recent findings indicated that mu- and kappa-opioid receptors enhance each other's antitussive processes. However, delta-opioid receptors played an inhibitory role in antitussive processes mediated by the mu- and kappa-opioid receptors. ⋯ These delta-opioid receptor-mediated antitussive effects may be mediated by the antagonism of delta(1)-, but not delta(2)-opioid receptors. In this review, we study the possibility of the delta-opioid receptor antagonist as a new concept for central acting antitussive drugs.