Our objective is to examine the mechanism of the additive/synergistic properties of b2-adrenoceptor stimulation and corticosteroid receptor activation in:
* Preventing neutrophil adhesion to specific endothelial ligands, e.g. ICAM-1 and
* Undergoing activation as a consequence of this adhesion.
We hypothesize that combination therapy with salmeterol + fluticasone (FP) will:
* Augment the inhibition of adhesion of neutrophils obtained from the peripheral blood of study subjects in vitro, by blocking gIV-PLA2 translocation to the nuclear membrane as for eosinophils;
* Augment the inhibition of transendothelial migration of neutrophils into airways of subjects with chronic obstructive pulmonary disease;
* Augment the numbers and concentrations of pro-inflammatory products in the bronchoalveolar lavage fluid; and
* Decrease the number of neutrophils in the bronchial tissue of endobronchial biopsies of treated patients.
