Budesonide but not terbutaline decreases phagocytosis in alveolar macrophages.
Alveolar macrophages are the most common cells in bronchoalveolar lavage fluid. The macrophages participate in the inflammatory response and defence of the airways by secretion of mediators and by phagocytizing foreign particles such as bacteria and viruses. beta-Agonists and glucocorticosteroids are the most frequently used drugs in asthma. Alveolar macrophages have beta 2-adrenoceptors on their surface but the functional role of these receptors is unknown. Glucocorticosteroids interact with mediator release from macrophages. However, nothing is known about the effects of those drugs on the phagocytic capacity of alveolar macrophages. Therefore, the present study has investigated phagocytosis of alveolar macrophages from nine healthy volunteers after incubation with a beta 2-agonist, terbutaline (10(-8), 10(-6) and 10(-4) M) and a glucocorticosteroid, budesonide (10(-9), 10(-7) and 10(-5) M). Alveolar macrophages were incubated with FITC-labelled Escherichia coli, and the drugs and phagocytosis was assessed by flow cytometry. Phagocytosis was measured as the proportion of phagocytizing cells and mean fluorescence intensity (MFI). MFI was highly correlated with phagocytized E. coli per cell assessed by fluorescence microscopy (r = 0.996). The proportion of phagocytizing macrophages (control) was [median (25th-75th) percentiles] 46% (40-63) and 29% (18-60), and MFI were 174 (154-205) and 122 (90-271) in the terbutaline and budesonide experiments, respectively. Terbutaline did not affect the phagocytosis significantly, while budesonide decreased the phagocytic capacity (percent phagocytizing cells and MFI) in a dose-dependent manner (P < 0.01). At the highest budesonide concentration (10(-5) M), phagocytosis was approximately half of the control situation. In conclusion, this in vitro study indicate that a glucocorticosteroid decreases phagocytosis in alveolar macrophages in a concentration that may be relevant in the airway lining fluid. Further investigations regarding the effect on other micro-organisms and in vivo effects are necessary to further elucidate these findings.
Zetterlund
A
A
Department of Thoracic Medicine, Karolinska Hospital, Stockholm, Sweden.
Larsson
P H
PH
Müller-Suur
C
C
Palmberg
L
L
Larsson
K
K
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D019819:Budesonide / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis / Q000187:drug effects*; D013015:Sotalol / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000893:Anti-Inflammatory Agents; D019819:Budesonide; D013015:Sotalol; D013726:Terbutaline