title: Temporal neutrophil polarization following myocardial infarction.
abstract: OBJECTIVE
  Although macrophage phenotypes have been well studied in the myocardial infarction (MI) setting, this study investigated temporal neutrophil polarization and activation mechanisms.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA mllindsey@umc.edu yma@umc.edu.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Andriy
authors.initials: A
authors.lastname: Yabluchanskiy
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Rugmani Padmanabhan
authors.initials: RP
authors.lastname: Iyer
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Presley L
authors.initials: PL
authors.lastname: Cannon
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Flynn
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Mira
authors.initials: M
authors.lastname: Jung
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Henry
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Courtney A
authors.initials: CA
authors.lastname: Cates
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA.
authors.forename: Kristine Y
authors.initials: KY
authors.lastname: Deleon-Pennell
authors.affiliation: San Antonio Cardiovascular Proteomics Center and Mississippi Center for Heart Research, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505, USA Research Service, G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS 39216, USA mllindsey@umc.edu yma@umc.edu.
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
mesh_terms: D000818:Animals; D016764:Cell Polarity; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism*; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D015847:Interleukin-4; D007371:Interferon-gamma
keywords: DAMPs; Inflammation; Myocardial infarction; Neutrophil polarization; Proteomics
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