Temporal neutrophil polarization following myocardial infarction

Cardiovasc Res. 2016 May 1;110(1):51-61. doi: 10.1093/cvr/cvw024. Epub 2016 Jan 29.


Aims: Although macrophage phenotypes have been well studied in the myocardial infarction (MI) setting, this study investigated temporal neutrophil polarization and activation mechanisms.

Methods and results: Neutrophils isolated from the infarcted left ventricle (LV) of mice showed high expression of proinflammatory markers at Day 1 and anti-inflammatory markers at Days 5 and 7 post-MI, indicating distinct neutrophil phenotypes along the post-MI time continuum. Flow cytometry analysis revealed that although proinflammatory N1 neutrophils were always predominant (>80% of total neutrophils at each time point), the percentage of N2 neutrophils increased post-MI from 2.4 ± 0.6% at Day 1 to 18.1 ± 3.0% at Day 7. In vitro, peripheral blood neutrophils were polarized to proinflammatory N1 by lipopolysaccharide and interferon-γ or anti-inflammatory N2 by interleukin-4, indicating high plasticity potential. The in vivo post-MI relevant LV damage-associated molecular patterns (DAMPs) polarized neutrophils to a proinflammatory N1 phenotype by activating toll-like receptor-4. Transforming growth factor-β1 inhibited proinflammatory production in neutrophils. N1 neutrophils positively correlated with infarct wall thinning at Day 7 post-MI, possibly due to high production of matrix metalloproteinases-12 and -25.

Conclusion: This study is the first to identify the existence of N1 and N2 neutrophils in the infarct region and reveals that N1 polarization could be mediated by DAMPs.

Keywords: DAMPs; Inflammation; Myocardial infarction; Neutrophil polarization; Proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Polarity
  • Disease Models, Animal
  • Inflammation / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Macrophages / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Neutrophils / metabolism*
  • Ventricular Remodeling / physiology*


  • Interleukin-4
  • Interferon-gamma