beta 2-agonist-induced inhibition of neutrophil chemotaxis is not associated with modification of LFA-1 and Mac-1 expression or with impairment of polymorphonuclear leukocyte antibacterial activity.
Patients with chronic obstructive lung disorders often show increased susceptibility to airway infections. As beta 2-adrenoceptor agonists, in addition to reversing the contractile response of bronchial smooth muscles, may inhibit a variety of inflammatory and immuno-effector cell functions, it is possible that these drugs interfere with host defence mechanisms. The present study was designed to test in vitro whether fenoterol, a short-acting beta 2-adrenoceptor agonist, could modify human blood neutrophil recruitment and antimicrobial activity. Pre-exposure to fenoterol significantly reduced neutrophil migration towards the complement component C5a, at concentrations ranging from 10(-7) M to 10(-5) M, or towards lipopolysaccharide, at a concentration of 10(-5) M (P < 0.05, each comparison). In contrast, the drug (10(-8)-10(-5) M) did not significantly modify the increased expression of lymphocyte function-associated antigen (LFA-1, i.e. CD11a/CD18) the macrophage antigen-1 (Mac-1, i.e. CD11b/CD18) induced by N-formylmethionylleucylphenylalanine (fMLP) (P > 0.05, each comparison). Finally, incubation of neutrophils with fenoterol (10(-8)-10(-5) M) did not significantly influence phagocytosis or intracellular killing of bacteria (Staphylococcus aureus) or H2O2 release induced by tetradecanoyl-phorbol-acetate (P > 0.1 for each comparison). These results suggest that short-acting beta 2-adrenoceptor agonists, such as fenoterol, are able partially to reduce neutrophil recruitment in the airways without interfering with the processes involved in phagocytic activity against bacteria.
Silvestri
M
M
Divisione di Pneumologia, Istituto G. Gaslini, Genoa, Italy.
Oddera
S
S
Lantero
S
S
Rossi
G A
GA
D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D005260:Female; D005280:Fenoterol / Q000494:pharmacology*; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology*; D011941:Receptors, Adrenergic / Q000276:immunology
D000318:Adrenergic beta-Agonists; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D011941:Receptors, Adrenergic; D005280:Fenoterol