Background: Besides being highly effective in the treatment of allergic and nonallergic rhinitis with eosinophilia, intranasal corticosteroids appear to be useful in reducing nasal polypoid lesions and the likelihood of polyp recurrence after surgery. We evaluated the ability of fluticasone propionate to downregulate fibroblast functions related to nasal inflammation and remodeling. Methods: Primary nasal polyp tissue-derived fibroblasts were stimulated with tumor necrosis factor (TNF)-α or interleukin (IL)-4 or basic fibroblast growth factor (bFGF) in the presence of fluticasone propionate (0.1–100 nM). Fibroblast proliferation, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression and eotaxin release were then evaluated. Results: As compared with unstimulated cultures, a significant increase in fibroblast proliferation was observed when the cells were stimulated with bFGF (p < 0.05), but not with TNF-α or IL-4 (p > 0.05). TNF-α induced an upregulation of ICAM-1 expression (p < 0.05), which was not seen in fibroblasts cultured in the presence of IL-4 or bFGF. No changes in VCAM-1 expression were induced by TNF-α, IL-4 or bFGF, whereas both TNF-α and IL-4 increased eotaxin release (p < 0.05). Both bFGF-induced fibroblast proliferation and TNF-α-induced ICAM-1 expression were significantly reduced by fluticasone, starting at the dose of 1 and 10 nM, respectively (p < 0.05). Fluticasone at concentrations of 1–100 nM effectively inhibited eotaxin release by TNF-α- or IL-4-stimulated fibroblasts (p < 0.05). Conclusions: The pharmacologic activity of fluticasone in patients with chronic upper airway inflammatory disease may include inhibition of resident fibroblast functions involved in airway inflammation and remodeling.

Allergic asthma is characterized by eosinophil migration in the airways, which is strictly dependent on the expression of adhesion molecules. This study investigated whether the expression of adhesion molecules on eosinophils is increased and associated with disease activity in allergic asthma. Twenty atopic asthmatic (AA) subjects and nine controls were studied and the expression of lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), Mac-1 (CD11b/CD18) and very late antigen-4 (VLA-4; CD49d/CD29) on blood eosinophils was evaluated by specific monoclonal antibody (Mab) staining and flow-cytometric analysis. Compared with controls, eosinophils from AA showed increased expression of LFA-1 (p<0.005), but not of Mac-1 or VLA-4 (p>0.1). In addition, LFA-1 expression correlated positively with blood eosinophil number (r=0.792, p<0.05), while no correlations were observed between Mac-1 or VLA-4 expression and blood eosinophil number. The migration of eosinophils through human umbilical vein endothelial cells with or without anti-LFA-1, Mac-1 and VLA-4-blocking Mab was studied. Compared with controls, eosinophils from AA showed increased migration toward C5a (p<0.01). Cell migration was totally inhibited by preincubating eosinophils with anti-LFA-1 (p<0.05), while anti-Mac-1 had no effect (p>0.1). Thus, the expression of lymphocyte function-associated antigen-1 by blood eosinophils is increased in atopic asthmatics and seems to modulate the enhanced eosinophil migration observed in allergic asthma.

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Summary. AC1331 cells may represent an alternative source of transplantable haemopoietic progenitor cells to CD34 1 cells. Here, we have addressed the characterization of umbilical cord blood (UCB) AC1331 cells and compared their immunophenotypic and functional features with those of UCB CD34 1 cells. UCB AC133 1 and CD34 1 cell fractions were purified by magnetic cell sorting, analysed by flow cytometry, tested for their content in blast cell colonyforming units (CFU-Bl), erythroid and granulocyte±macro-phage colony-forming units before and after expansion in the presence of various haemopoietic growth factor combinations. Median AC133 1 cell yield was 62´3%, and median AC133 1 population purity was 97´9%. AC133 1 cells were found to contain significantly more CFU-Bl than CD34 1 cells; furthermore, the replating efficiency, i.e. the number of CFU-Bl capable of generating secondary colonies, was higher in the former than in the latter cells. Both AC133 1 and CD34 1 cells displayed an increased ability to give rise to committed progenitors after 7-day expansion in liquid cultures. These data suggest that the AC133 1 cell subset is a heterogeneous pool of immature and more differentiated cells that can be maintained and expanded in well-defined culture conditions. In comparison with CD34 1 cells, UCB AC1331 cells appear to contain a higher number of early haemopoietic progenitors.