Download PDF
Thromb Haemost 2015; 113(03): 473-481
DOI: 10.1160/TH14-06-0507
Theme Issue Article
Schattauer GmbH

Regulation of monocyte/macrophage polarisation by extracellular RNA

Hector A. Cabrera-Fuentes
1   Institute of Biochemistry, Medical School, Justus-Liebig University, Giessen, Germany
2   Department of Microbiology, Kazan Federal University, Kazan, Russian Federation
,
Mercedes L. Lopez
3   Instituto Venezolano de Investigaciones Cientficas, Centro de Biofísica y Bioquímica, Caracas, Venezuela
,
Sara McCurdy
4   Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA;
,
Silvia Fischer
1   Institute of Biochemistry, Medical School, Justus-Liebig University, Giessen, Germany
,
Svenja Meiler
5   Department of Medical Biochemistry, Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
,
Yvonne Baumer
4   Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA;
,
Sebastian P. Galuska
1   Institute of Biochemistry, Medical School, Justus-Liebig University, Giessen, Germany
,
Klaus T. Preissner   †
1   Institute of Biochemistry, Medical School, Justus-Liebig University, Giessen, Germany
2   Department of Microbiology, Kazan Federal University, Kazan, Russian Federation
,
William A. Boisvert   †
2   Department of Microbiology, Kazan Federal University, Kazan, Russian Federation
4   Center for Cardiovascular Research, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA;
› Author Affiliations
Further Information

Publication History

Received: 10 June 2014

Accepted after major revision: 28 January 2014

Publication Date:
29 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Monocytes/macrophages respond to external stimuli with rapid changes in the expression of numerous inflammation-related genes to undergo polarisation towards the M1 (pro-inflammatory) or M2 (antiinflammatory) phenotype. We have previously shown that, independently of Toll-like receptor activation, extracellular RNA (eRNA) could exert prothrombotic and pro-inflammatory properties in the cardiovascular system to provoke cytokine mobilisation. Here, mouse bone marrow-derived-macrophages (BMDM) differentiated with mouse macrophage-colony-stimulating factor (M-CSF) were found to be skewed towards the M1 phenotype when exposed to eRNA. This resulted in up-regulated expression of inflammatory markers such as Tnf-α and Il-6, together with Il-12 and iNOS, whereas anti-inflammatory genes such as chitinase-like proteins (Ym1/2) and macrophage mannose receptor-2 (Cd206) were significantly down-regulated. Human peripheral blood monocytes were treated with eRNA and analysed by micro-array analysis of the whole human genome, revealing an up-regulation of 79 genes by at least four-fold; 27 of which are related to signal transduction and 15 genes associated with inflammatory response. In accordance with the proposed actions of eRNA as a pro-inflammatory “alarm signal”, these data shed light on the role of eRNA in the context of chronic inflammatory diseases such as atherosclerosis.

Keywords

Extracellular RNA - inflammation - microarray technology - gene expression - monocyte/macrophage polarisation

† Drs Preissner and Boisvert contributed equally to this work as senior authors.


 

  • References

  • 1 Neu C, Sedlag A, Bayer C. et al. CD14-dependent monocyte isolation enhances phagocytosis of listeria monocytogenes by proinflammatory, GM-CSF-derived macrophages. PloS one 2013; 8: e66898.
    CrossrefPubMedSearch in Google Scholar
  • 2 Leitinger N, Schulman IG. Phenotypic polarisation of macrophages in atherosclerosis. Arterioscl Thromb Vasc Biol 2013; 33: 1120-1126.
    CrossrefPubMedSearch in Google Scholar
  • 3 Davis MJ, Tsang TM, Qiu Y. et al. Macrophage M1/M2 polarisation dynamically adapts to changes in cytokine microenvironments in Cryptococcus neoformans infection. mBio 2013; 4: e00264-13.
    PubMedSearch in Google Scholar
  • 4 Simsekyilmaz S, Cabrera-Fuentes HA, Meiler S. et al. Role of extracellular RNA in atherosclerotic plaque formation in mice. Circulation 2014; 129: 598-606.
    CrossrefPubMedSearch in Google Scholar
  • 5 Simsekyilmaz S, Cabrera-Fuentes HA, Meiler S. et al. Response to letter regarding article “role of extracellular RNA in atherosclerotic plaque formation in mice". Circulation 2014; 130: e144-145.
    CrossrefPubMedSearch in Google Scholar
  • 6 Fischer S, Grantzow T, Pagel JI. et al. Extracellular RNA promotes leukocyte recruitment in the vascular system by mobilising proinflammatory cytokines. Thromb Haemost 2012; 108: 730-741.
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Fischer S, Cabrera-Fuentes HA, Noll T. et al. Impact of extracellular RNA on endothelial barrier function. Cell Tissue Res. 2014 Epub ahead of print.
    PubMedSearch in Google Scholar
  • 8 Lopez ML, Bruges G, Crespo G. et al. Thrombin selectively induces transcription of genes in human monocytes involved in inflammation and wound healing. Thromb Haemost 2014; 112: 992-1001.
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Cabrera-Fuentes HA, Aslam M, Saffarzadeh M. et al. Internalisation of Bacillus intermedius ribonuclease (BINASE) induces human alveolar adenocarcinoma cell death. Toxicon 2013; 69: 219-226.
    CrossrefPubMedSearch in Google Scholar
  • 10 Saffarzadeh M, Juenemann C, Queisser MA. et al. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of hi-stones. PloS one 2012; 7: e32366.
    CrossrefPubMedSearch in Google Scholar
  • 11 Whyte CS, Bishop ET, Ruckerl D. et al. Suppressor of cytokine signallin g (SOCS)1 is a key determinant of differential macrophage activation and function. J Leuk Biol 2011; 90: 845-854.
    CrossrefPubMedSearch in Google Scholar
  • 12 Gao S, Wang L, Liu W. et al. The synergistic effect of homocysteine and lipo-polysaccharide on the differentiation and conversion of raw264.7 macrophages. J Inflam 2014; 11: 13.
    PubMedSearch in Google Scholar
  • 13 Dreschers S, Gille C, Haas M. et al. Infection-induced bystander-apoptosis of monocytes is TNF-alpha-mediated. PloS one 2013; 8: e53589.
    CrossrefPubMedSearch in Google Scholar
  • 14 Fischer S, Gesierich S, Griemert B. et al. Extracellular RNA liberates tumour necrosis factor-alpha to promote tumour cell trafficking and progression. Cancer Res 2013; 73: 5080-5089.
    CrossrefPubMedSearch in Google Scholar
  • 15 Colak G, Johnson GV. Complete transglutaminase 2 ablation results in reduced stroke volumes and astrocytes that exhibit increased survival in response to ischemia. Neurobiol Dis 2012; 45 1042-1050.
    PubMedSearch in Google Scholar
  • 16 Biswas P, Delfanti F, Bernasconi S. et al. Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line. Blood 1998; 91: 258-265.
    CrossrefPubMedSearch in Google Scholar
  • 17 Cabrera-Fuentes HA, Ruiz-Meana M, Simsekyilmaz S. et al. RNase1 prevents the damaging interplay between extracellular RNA and tumour necrosis factor-alpha in cardiac ischaemia/reperfusion injury. Thromb Haemost 2014; 112: 1110-1119.
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Dennis Jr. G, Sherman BT, Hosack DA. et al. DAVID: Database for Annotation, Visualisation, and Integrated Discovery. Genome Biol 2003; 4: P3.
    CrossrefPubMedSearch in Google Scholar
  • 19 Rhee SH, Jones BW, Toshchakov V. et al. Toll-like receptors 2 and 4 activate STAT1 serine phosphorylation by distinct mechanisms in macrophages. J Biol Chem 2003; 278: 22506-22512
    CrossrefPubMedSearch in Google Scholar