Distinct infiltration of neutrophils in lesion shoulders in ApoE-/- mice

Am J Pathol. 2010 Jul;177(1):493-500. doi: 10.2353/ajpath.2010.090480. Epub 2010 May 14.


Inflammation and activation of immune cells are key mechanisms in the development of atherosclerosis. Previous data indicate important roles for monocytes and T-lymphocytes in lesions. However, recent data suggest that neutrophils also may be of importance in atherogenesis. Here, we use apolipoprotein E (ApoE)-deficient mice with fluorescent neutrophils and monocytes (ApoE(-/-)/Lys(EGFP/EGFP) mice) to specifically study neutrophil presence and recruitment in atherosclerotic lesions. We show by flow cytometry and confocal microscopy that neutrophils make up for 1.8% of CD45(+) leukocytes in the aortic wall of ApoE(-/-)/Lys(EGFP/EGFP) mice and that their contribution relative to monocyte/macrophages within lesions is approximately 1:3. However, neutrophils accumulate at sites of monocyte high density, preferentially in shoulder regions of lesions, and may even outnumber monocyte/macrophages in these areas. Furthermore, intravital microscopy established that a majority of leukocytes interacting with endothelium on lesion shoulders are neutrophils, suggesting a significant recruitment of these cells to plaque. These data demonstrate neutrophilic granulocytes as a major cellular component of atherosclerotic lesions in ApoE(-/-) mice and call for further study on the roles of these cells in atherogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / cytology
  • Aorta / immunology
  • Aorta / pathology
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Atherosclerosis* / immunology
  • Atherosclerosis* / pathology
  • Bone Marrow Transplantation
  • Gene Knock-In Techniques
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / immunology
  • Humans
  • Leukocyte Rolling
  • Mice
  • Mice, Knockout
  • Monocytes / cytology
  • Monocytes / immunology
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Plaque, Atherosclerotic* / immunology
  • Plaque, Atherosclerotic* / pathology


  • Apolipoproteins E
  • Green Fluorescent Proteins