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Azithromycin Reduces Exaggerated Cytokine Production by M1 Alveolar Macrophages in Cystic Fibrosis
被引:99
作者:
Meyer, Magali
[1
]
Huaux, Francois
[2
]
Gavilanes, Ximena
[1
]
van den Brule, Sybille
[2
]
Lebecque, Patrick
[3
]
Lo Re, Sandra
[2
]
Lison, Dominique
[2
]
Scholte, Bob
[4
]
Wallemacq, Pierre
[1
]
Leal, Teresinha
[1
]
机构:
[1] Univ Catholique Louvain, Dept Clin Chem, Brussels, Belgium
[2] Univ Catholique Louvain, Unit Ind Toxicol & Occupat Med, Brussels, Belgium
[3] Univ Catholique Louvain, Div Paediat Pulmonol, Brussels, Belgium
[4] Erasmus MC, Dept Cell Biol, Rotterdam, Netherlands
关键词:
cystic fibrosis;
cystic fibrosis transmembrane conductance regulator;
inflammation;
macrophages;
azithromycin;
TRANSMEMBRANE CONDUCTANCE REGULATOR;
EARLY PULMONARY INFLAMMATION;
AIRWAY EPITHELIAL-CELLS;
LONG-TERM AZITHROMYCIN;
NITRIC-OXIDE;
CONTROLLED-TRIAL;
IN-VITRO;
LUNG;
CHEMOKINE;
EXPRESSION;
D O I:
10.1165/rcmb.2008-0155OC
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Macrophages phagocyte pathogenic microorganisms and orchestrate immune responses by producing a variety of inflammatory mediators. The cystic fibrosis (CF) transmembrane conductance regulator chloride channel has been reported to be of pivotal importance for macrophage functions. The exact phenotype and role of macrophages in CF is still unknown. Alveolar and peritoneal macrophages were monitored in CIF mice homozygous for the F508 del mutation and in wild-type control animals. Classical (M1) and alternative (M2) macrophage polarization and responses to LIPS from Pseudomonas aeruginosa were investigated, and the effect of azithromycin was examined in both cell populations. We show that alveolar macrophage counts were 1.7-fold higher in CIF as compared with wild-type mice. The macrophage-related chemokine, chemokine C-C motif ligand (CCL)-2, was found to be at least 10-fold more abundant in the alveolar space of mutant mice. Cell count and CCL-2 protein levels were also increased in the peritoneal cavity of CIF mice. Both M1 and M2 macrophage polarization were significantly enhanced in alveolar and peritoneal cells from F508del-CF mice as compared with control animals. LPS-stimulated expression of proinflammatory mediators, such as nitric oxide synthase-2, IL-1 beta, and CCL-2, was increased, whereas anti-inflammatory IL-10 expression was decreased in CIF macrophages. Azithromycin, added to cell cultures at 1 mg/liter, significantly reduced proinflammatory cytokine expression (IL-1 beta, CCL-2, TNF-alpha) in M1-induced CF and wild-type alveolar macrophages. Our findings indicate that CF macrophages are ubiquitously accumulated, and that these cells are polarized toward classical and alternative activation status. Azithromycin down-regulates inflammatory cytokine production by M1-polarized CIF alveolar macrophages.
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页码:590 / 602
页数:13
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