Ozone primes alveolar macrophage–derived innate immunity in healthy human subjects

Consistent with animal studies, evidence from sputum macrophages isolated from humans exposed to ozone identified enhanced surface expression of TLR4 and CD14 by flow cytometry.2-4 However, the functional relevance of these initial observations in healthy human subjects remained unknown. [...]the pr...

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Bibliographic Details
Published inJournal of allergy and clinical immunology Vol. 138; no. 4; pp. 1213 - 1215.e1
Main Authors Frush, Benjamin W., Li, Zhuowei, Stiles, Jane V., Cotter, Sarah F., Shofer, Scott L., Foster, W. Michael, Hollingsworth, John W., Tighe, Robert M.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.10.2016
Elsevier Limited
Subjects
Administration, Inhalation
Adult
Allergy and Immunology
Animals
Body mass index
Female
Genes
Healthy Volunteers
Human subjects
Humans
Immunity, Innate - drug effects
Immunity, Innate - genetics
Immunity, Innate - physiology
In Vitro Techniques
Kinases
Laboratories
Lipopolysaccharide Receptors - genetics
Lipopolysaccharides - pharmacology
Macrophages, Alveolar - drug effects
Macrophages, Alveolar - immunology
Macrophages, Alveolar - metabolism
Male
Mice
Ozone - administration & dosage
Ozone - pharmacology
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Tetradecanoylphorbol Acetate - pharmacology
Toll-Like Receptor 4 - genetics
Young Adult
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Summary:Consistent with animal studies, evidence from sputum macrophages isolated from humans exposed to ozone identified enhanced surface expression of TLR4 and CD14 by flow cytometry.2-4 However, the functional relevance of these initial observations in healthy human subjects remained unknown. [...]the present study was designed to test the hypothesis that in vivo inhalation of relevant levels of ambient ozone would enhance human alveolar macrophage responses ex vivo to bacterial stimulation with LPS. To determine innate immune response, cultured cells were stimulated with bacterial LPS, which is a prototypic TLR4-dependent ligand.6 Cells were also challenged with phorbol-12-myristate-13-acetate (PMA), a specific activator of protein kinase C, which is directly involved in intracellular TLR signaling,7 but does not require intact surface TLR4.
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ISSN:0091-6749
1097-6825
1097-6825
DOI:10.1016/j.jaci.2016.03.052