Distinct infiltration of neutrophils in lesion shoulders in ApoE-/- mice.
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.
Rotzius
Pierre
P
Departments of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Thams
Sebastian
S
Soehnlein
Oliver
O
Kenne
Ellinor
E
Tseng
Chi-Nan
CN
Björkström
Niklas K
NK
Malmberg
Karl-Johan
KJ
Lindbom
Lennart
L
Eriksson
Einar E
EE
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation; D055879:Gene Knock-In Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D036904:Leukocyte Rolling; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000473:pathology
D001057:Apolipoproteins E; D049452:Green Fluorescent Proteins
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