title: Differential in vivo activation of monocyte subsets during low-grade inflammation through experimental endotoxemia in humans.
abstract: Human monocytes are a heterogeneous cell population, which can be divided into a classical (CD14++CD16-), a non-classical (CD14+CD16+), and an intermediate (CD14++CD16+) subset. We hypothesized that low-grade inflammation may differentially affect monocyte subsets. We used a human lipopolysaccharide (LPS) infusion model to mimic low-grade inflammation to identify, which monocyte subsets are preferentially activated under these conditions. Monocyte subsets were identified by staining for CD14 and CD16, activation status of monocytes was analyzed by staining for CD11b and a novel in situ mRNA hybridization approach to detect IL-6 and IL-8 specific mRNA at the single-cell level by flow cytometry. After LPS challenge, cell numbers of monocyte subsets dropped after 2 h with cell numbers recovering after 6 h. Distribution of monocyte subsets was skewed dramatically towards the intermediate subset after 24 h. Furthermore, intermediate monocytes displayed the largest increase of CD11b expression after 2 h. Finally, IL-6 and IL-8 mRNA levels increased in intermediate and non-classical monocytes after 6 h whereas these mRNA levels in classical monocytes changed only marginally. In conclusion, our data indicates that the main responding subset of monocytes to standardized low-grade inflammation induced by LPS in humans is the CD14++CD16+ intermediate subset followed by the CD14+CD16+ non-classical monocyte subset. Circulating classical monocytes showed comparably less reaction to LPS challenge in vivo.
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Thaler
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: P J
authors.initials: PJ
authors.lastname: Hohensinner
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria.
authors.forename: K A
authors.initials: KA
authors.lastname: Krychtiuk
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Matzneller
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: L
authors.initials: L
authors.lastname: Koller
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Brekalo
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Maurer
authors.affiliation: 3rd Medical Department for Cardiology and Emergency Medicine, Wilhelminen Hospital, Vienna, Austria.
authors.forename: K
authors.initials: K
authors.lastname: Huber
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Zeitlinger
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Jilma
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.|Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria.|Core Facilities, Medical University of Vienna, Vienna, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Wojta
authors.affiliation: Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
authors.forename: W S
authors.initials: WS
authors.lastname: Speidl
mesh_terms: D002452:Cell Count / Q000379:methods; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017452:Receptors, IgG