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Human monocytes and macrophages differ in their mechanisms of adaptation to hypoxia

Overview of attention for article published in Arthritis Research & Therapy, January 2012
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Title
Human monocytes and macrophages differ in their mechanisms of adaptation to hypoxia
Published in
Arthritis Research & Therapy, January 2012
DOI 10.1186/ar4011
Pubmed ID
Authors

Monique Fangradt, Martin Hahne, Timo Gaber, Cindy Strehl, Roman Rauch, Paula Hoff, Max Löhning, Gerd-Rüdiger Burmester, Frank Buttgereit

Abstract

ABSTRACT: INTRODUCTION: Inflammatory arthritis is a progressive disease with chronic inflammation of joints, which is mainly characterized by the infiltration of immune cells and synovial hyperproliferation. Monocytes migrate towards inflamed areas and differentiate into macrophages. In inflamed tissues, much lower oxygen levels (hypoxia) are present in comparison to the peripheral blood. Hence, a metabolic adaptation process must take place. Other studies suggest that Hypoxia Inducible Factor 1-alpha (HIF-1α) may regulate this process, but the mechanism involved for human monocytes is not yet clear. To address this issue, we analyzed the expression and function of HIF-1α in monocytes and macrophages, but also considered alternative pathways involving nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFκB). METHODS: Isolated human CD14+ monocytes were incubated under normoxia and hypoxia conditions with or without phorbol 12-myristate 13-acetate (PMA) stimulation, respectively. Nuclear and cytosolic fractions were prepared in order to detect HIF-1α and NFκB by immunoblot. For the experiments with macrophages, primary human monocytes were differentiated into human monocyte derived macrophages (hMDM) using human macrophage colony-stimulating factor (hM-CSF). The effects of normoxia and hypoxia on gene expression were compared between monocytes and hMDMs using quantitative PCR (quantitative polymerase chain reaction). RESULTS: We demonstrate, using primary human monocytes and hMDM, that the localization of transcription factor HIF-1α during the differentiation process is shifted from the cytosol (in monocytes) into the nucleus (in macrophages), apparently as an adaptation to a low oxygen environment. For this localization change, protein kinase C alpha/beta 1 (PKC-α/β1 ) plays an important role. In monocytes, it is NFκB1, and not HIF-1α, which is of central importance for the expression of hypoxia-adjusted genes. CONCLUSIONS: These data demonstrate that during differentiation of monocytes into macrophages, crucial cellular adaptation mechanisms are decisively changed.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 71 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 1%
Unknown 70 99%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 28%
Student > Master 14 20%
Researcher 7 10%
Student > Bachelor 6 8%
Professor > Associate Professor 4 6%
Other 8 11%
Unknown 12 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 18 25%
Biochemistry, Genetics and Molecular Biology 11 15%
Medicine and Dentistry 9 13%
Immunology and Microbiology 7 10%
Business, Management and Accounting 2 3%
Other 8 11%
Unknown 16 23%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 August 2012.
All research outputs
#7,813,286
of 12,451,992 outputs
Outputs from Arthritis Research & Therapy
#1,414
of 1,983 outputs
Outputs of similar age
#69,105
of 122,375 outputs
Outputs of similar age from Arthritis Research & Therapy
#3
of 3 outputs
Altmetric has tracked 12,451,992 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,983 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one is in the 20th percentile – i.e., 20% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 122,375 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one.