Löms Ziegler-Heitbrock

University of Leicester

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Marion Frankenberger

Asklepios Fachkliniken München-Gauting

Reinhard Hoffmann

Berufsgenossenschaftliche Unfallklinik Frankfurt am Main

Thomas Höfer

Heidelberg University

Thomas P. Hofer

Helmholtz Zentrum München

K Häußinger

Asklepios Fachkliniken München-Gauting

Winfried Möller

Helmholtz Association of German Research Centres

Irene Heimbeck

Inamed

Roland Lang

Urologische Klinik München

Kai-Uwe Belge

Institute of Immunology

Alexia Horelt

Hôpital Nord

Cooperative Institutions

Ludwig-Maximilians-Universität München

Helmholtz Zentrum München

Asklepios Fachkliniken München-Gauting

LMU Klinikum

German Center for Lung Research

University of Leicester

München Klinik

Jagiellonian University

Technical University of Munich

Institute of Immunology

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Intermediate CD14++CD16+ blood monocytes are elevated in preterm neonates

European Respiratory Journal (2014)

Marion Frankenberger Gudrun Kaßner Prajakta Oak Kai Förster Harald Ehrhardt

Monocytes are a major part of the innate immune system. Three populations of blood monocyte subsets in humans have been defined according to their differential expression of CD14 and CD16: classical CD14++CD16-, non-classical CD14+CD16++ and intermediate CD14++CD16+ monocytes. In adults these subsets are well described, but very little is known on the development and activity of these cells in very-preterm neonates. Blood samples from preterm neonates born at gestational age from 24 to 32 weeks were taken from day 0 up to 11 weeks after birth and compared with term neonates born by cesarean section and adult controls. At 10 days or less after birth intermediate CD14++CD16+ monocytes were strongly elevated in preterm neonates (49.1±9.2% of all monocytes at 24-26 weeks gestational age), they were still high at 20.7±6.3 % in preterm neonates born at 30-32 weeks gestational age while in term neonates they accounted for 6.9±3.3% compared to 3.3±0.98% in adult control donors. CD62L expression was 4-fold higher in intermediate monocytes from preterm neonates compared to cells from term neonates and adults, but HLA-DR was strongly decreased in preterm intermediate monocytes. While both intermediate monocytes and non-classical monocytes were strong producers of Lipopolysaccharide induced-TNF in preterm and term neonates the level of TNF production was 5-fold lower compared to what is seen in adult monocyte subsets. The strong expansion and aberrant phenotype of intermediate monocytes in preterm neonates may be explained by the immaturity of the innate immune system in the preterms and this may contribute to the increased susceptibility to infection.

CD16

Monocyte

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Citations (4)

Increased levels of soluble serum interleukin-2 receptor in extrinsic allergic alveolitis correlate with interleukin-2 receptor expression on alveolar macrophages

Journal of Allergy and Clinical Immunology (1994)

A Pforte Angela Brunnera P. Gais M Ströbel Georg Burger

Pulmonary alveolus

Alveolar macrophage

Extrinsic Allergic Alveolitis

10.1016/0091-6749(94)90124-4

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Citations (6)

Protective role of NF-κB1 (p50) in experimental pneumococcal meningitis

European Journal of Pharmacology (2004)

Stefan Kastenbauer Uwe Koedel Falk Weih Löms Ziegler-Heitbrock Hans‐Walter Pfister

10.1016/j.ejphar.2004.07.081

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Citations (23)

Murine serine proteases MASP-1 and MASP-3, components of the lectin pathway activation complex of complement, are encoded by a single structural gene

Genes and Immunity (2003)

Cordula Stover Nicholas J. Lynch Mads Ronald Dahl Steven Hanson Minoru Takahashi

Lectin pathway

MASP1

Complement component 2

C-type lectin

Ficolin

CD69

10.1038/sj.gene.6363970

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Citations (18)

The CD14+CD16+ monocytes in erysipelas are expanded and show reduced cytokine production

European Journal of Immunology (2002)

Alexia Horelt Kai-Uwe Belge Birgit Steppich Jörg C. Prinz Löms Ziegler-Heitbrock

In human peripheral blood the classical CD14++DR+ monocytes and the pro-inflammatory CD14+CD16+DR++ monocytes can be distinguished. In erysipelas we found strongly increased numbers of CD14+CD16+ monocytes on the day of diagnosis (day 1) in 11 patients with an average of 150.5±76.0 cells/μl, while 1 patient had low levels (35 cells/μl, control donors 48.8±19.8 cells/μl). The classical monocytes were only moderately elevated in the erysipelas patients (factor 1.7 as compared to controls). Patients exhibited increased body temperature, erythrocyte sedimentation rate and increased serum levels for C-reactive protein (CRP), IL-6 and macrophage-colony-stimulating factor. Among these, body temperature and CRP showed a significant correlation to the numbers of CD14+CD16+ monocytes. In 4 of 4 patients with high levels of CD14+CD16+ monocytes, these levels returned to that seen in controls by day 5 of antibiotic therapy. Determination of intracellular TNF was performed by three-color immunofluorescence and flow cytometry after ex vivo stimulation withlipoteichoic acid, a typical constituent of streptococci. Here, patient CD14+DR++ pro-inflammatory monocytes showed a twofold lower level of intracellular TNF. By contrast, expression of TNF was unaltered in the classical CD14++ monocytes. These data show that in erysipelas the pro-inflammatory CD14+CD16+DR++ monocytes are substantially expanded and selectively tolerant to stimulation by streptococcal products.

CD16

Erysipelas

Monocyte

10.1002/1521-4141(200205)32:5<1319::aid-immu1319>3.0.co;2-2

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Citations (69)

The Proinflammatory CD14+CD16+DR++ Monocytes Are a Major Source of TNF

The Journal of Immunology (2002)

Kai-Uwe Belge Farshid Dayyani Alexia Horelt Maciej Siedlar Marion Frankenberger

In human blood two monocyte populations can be distinguished, i.e., the CD14(++)CD16(-)DR(+) classical monocytes and the CD14(+)CD16(+)DR(++) proinflammatory monocytes that account for only 10% of all monocytes. We have studied TNF production in these two types of cells using three-color immunofluorescence and flow cytometry on whole peripheral blood samples stimulated with either LPS or with the bacterial lipopeptide S-(2,3-bis(palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys(4)-OH,trihydrochloride (Pam3Cys). After stimulation with LPS the median fluorescence intensity for TNF protein was 3-fold higher in the proinflammatory monocytes when compared with the classical monocytes. After stimulation with Pam3Cys they almost exclusively responded showing 10-fold-higher levels of median fluorescence intensity for TNF protein. The median fluorescence intensity for Toll-like receptor 2 cell surface protein was found 2-fold higher on CD14(+)CD16(+)DR(++) monocytes, which may explain, in part, the higher Pam3Cys-induced TNF production by these cells. When analyzing secretion of TNF protein into the supernatant in PBMCs after depletion of CD16(+) monocytes we found a reduction of LPS-induced TNF by 28% but Pam3Cys-induced TNF was reduced by 64%. This indicates that the minor population of CD14(+)CD16(+) monocytes are major producers of TNF in human blood.

Proinflammatory cytokine

CD16

Monocyte

10.4049/jimmunol.168.7.3536

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Citations (849)

Ingersoll MA, Spanbroek R, Lottaz C, et al. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood. 2010;115(3):e10–e19.

Blood (2010)

Molly A. Ingersoll Rainer Spanbroek Claudio Lottaz Emmanuel L. Gautier Marion Frankenberger

Monocyte

Human blood

10.1182/blood-2010-06-290122

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Citations (4)

Diesel exhaust particles increase LPS-stimulated COX-2 expression and PGE2 production in human monocytes

Journal of Leukocyte Biology (2004)

Thomas Höfer Ellen Bitterle Ingrid Beck‐Speier Konrad Maier Marion Frankenberger

Little is known about health effects of ultrafine particles (UFP) found in ambient air, but much of their action may be on cells of the lung, including cells of the monocyte/macrophage lineage. We have analyzed the effects of diesel exhaust particles (DEP; SRM1650a) on human monocytes in vitro. DEP, on their own, had little effect on cyclooxygenase (COX)-2 gene expression in the Mono Mac 6 cell line. However, when cells were preincubated with DEP for 1 h, then stimulation with the Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) induced an up-to fourfold-higher production of COX-2 mRNA with an average twofold increase. This costimulatory effect of DEP led to enhanced production of COX-2 protein and to increased release of prostaglandin E(2) (PGE(2)). The effect was specific in that tumor necrosis factor gene expression was not enhanced by DEP costimulation. Furthermore, costimulation with the TLR2 ligand Pam3Cys also led to enhanced COX-2 mRNA. DEP and LPS showed similar effects on COX-2 mRNA in primary blood mononuclear cells, in highly purified CD14-positive monocytes, and in monocyte-derived macrophages. Our data suggest that UFP such as DEP may exert anti-inflammatory effects mediated by enhanced PGE(2) production.

Monocyte

CD16

10.1189/jlb.0803387

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Citations (36)

Hyaluronan carried by tumor-derived microvesicles induces IL-10 production in classical (CD14 ++ CD16 − ) monocytes via PI3K/Akt/mTOR-dependent signalling pathway

Immunobiology (2015)

Marzena Lenart Magdalena Rutkowska-Zapała Monika Baj‐Krzyworzeka Rafał Szatanek Kazimierz Węglarczyk

Monocyte

10.1016/j.imbio.2015.06.019

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Citations (33)

Inhaled all-trans retinoic acid in an individual with severe emphysema: Table 1—

European Respiratory Journal (2009)

Marion Frankenberger Irene Heimbeck Winfried Möller Srinivas Mamidi Gudrun Kaßner

Introduction: Standard treatment for patients with Chronic Obstructive Pulmonary Disease (COPD) includes inhalers. 80% of them are not adherent to inhaled therapies, missing doses or not using medications correctly. Objective: To determine the effects of an educational intervention in the handling of inhalers in patients hospitalized due to acute exacerbation of COPD (AECOPD). Methods: In this clinical trial, patients were randomized into two groups. The control group received the standard medical treatment, and the intervention group received additionally a comprehensive education programme. Patients were evaluated at admission and discharge, outcome measures included forced expiratory volume in first second, peak flow, inhaler checklist and five times sit to stand test. Results: 15 patients were included. No significant differences between groups were found at baseline. Data expressed in mean±SD. *p<0,05. **p≤0,001. FEV1, Forced expiratory volume in the first second. Conclusion: An educational intervention in the handling of inhalers improves significantly the inhaler technique and the peak expiratory flow in AECOPD patients.

Group B

10.1183/09031936.00105309

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Citations (20)