| Azithromycin alters macrophage phenotype and pulmonary compartmentalization during lung infection with Pseudomonas. | |
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MedLine Citation:
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PMID: 20231397 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Infection with mucoid strains of Pseudomonas aeruginosa in chronic inflammatory diseases of the airway is difficult to eradicate and can cause excessive inflammation. The roles of alternatively activated and regulatory subsets of macrophages in this pathophysiological process are not well characterized. We previously demonstrated that azithromycin induces an alternatively activated macrophage-like phenotype in vitro. In the present study, we tested whether azithromycin affects the macrophage activation status and migration in the lungs of P. aeruginosa-infected mice. C57BL/6 mice received daily doses of oral azithromycin and were infected intratracheally with a mucoid strain of P. aeruginosa. The properties of macrophage activation, immune cell infiltration, and markers of pulmonary inflammation in the lung interstitial and alveolar compartments were evaluated postinfection. Markers of alternative macrophage activation were induced by azithromycin treatment, including the surface expression of the mannose receptor, the upregulation of arginase 1, and a decrease in the production of proinflammatory cytokines. Additionally, azithromycin increased the number of CD11b(+) monocytes and CD4(+) T cells that infiltrated the alveolar compartment. A predominant subset of CD11b(+) cells was Gr-1 positive (Gr-1(+)), indicative of a subset of cells that has been shown to be immunoregulatory. These differences corresponded to decreases in neutrophil influx into the lung parenchyma and alteration of the characteristics of peribronchiolar inflammation without any change in the clearance of the organism. These results suggest that the immunomodulatory effects of azithromycin are associated with the induction of alternative and regulatory macrophage activation characteristics and alteration of cellular compartmentalization during infection. |
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Authors:
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David J Feola; Beth A Garvy; Theodore J Cory; Susan E Birket; Heather Hoy; Don Hayes; Brian S Murphy |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-15 |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 54 ISSN: 1098-6596 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-18 Completed Date: 2010-09-14 Revised Date: 2011-03-03 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: United States |
Other Details:
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Languages: eng Pagination: 2437-47 Citation Subset: IM |
Affiliation:
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Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY 43536-0082, USA. djfeol2@email.uky.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anti-Bacterial Agents / pharmacology* Antigens, CD11b / metabolism Antigens, CD11c / metabolism Azithromycin / pharmacology* CD4-Positive T-Lymphocytes / drug effects, immunology Cytokines / biosynthesis Lung / drug effects, immunology, pathology Macrophage Activation / drug effects* Mice Mice, Inbred C57BL Monocytes / drug effects, immunology Phenotype Pneumonia, Bacterial / drug therapy*, immunology*, pathology Pseudomonas Infections / drug therapy*, immunology*, pathology Pseudomonas aeruginosa |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 0/Antigens, CD11b; 0/Antigens, CD11c; 0/Cytokines; 83905-01-5/Azithromycin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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