Accumulation of myeloperoxidase-positive neutrophils in atherosclerotic lesions in LDLR-/- mice.
OBJECTIVE
Atherosclerosis is a chronic inflammatory disease in which the immune system plays an important role. Neutrophils have not been thoroughly studied in the context of atherogenesis. Here, we investigated neutrophils in the development of murine atherosclerotic lesions.


RESULTS
LDLR-/- mice were given a high-fat diet for different time periods and subsequently atherosclerotic lesions were studied by immunohistochemistry. Staining with anti-Ly-6G monoclonal antibody, a specific marker for neutrophils, revealed a marked accumulation of neutrophils during atherosclerosis development. Neutrophils were observed in the lesion, attached to the cap, and in the arterial adventitia. In addition, at some sites, neutrophil accumulation colocalized with endothelial E-selectin expression. Immunofluorescence double staining with anti-myeloperoxidase and anti-Ly-6G antibodies demonstrated the presence of myeloperoxidase in atherosclerotic lesions and its colocalization with neutrophils. After introducing the high-fat diet, levels of circulating myeloperoxidase in plasma strongly increased, with a peak at 6 weeks and a subsequent decrease to almost normal levels after 16 weeks of diet.


CONCLUSIONS
We here demonstrate for the first time the presence of neutrophils and myeloperoxidase in murine atherosclerotic lesions. As a major cell type in inflammatory responses the neutrophil may also be an important mediator in the development of atherosclerosis.
van Leeuwen
Marcella
M
Department of Clinical and Experimental Immunology, Cardiovascular Research Institute Maastricht, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Gijbels
Marion J J
MJ
Duijvestijn
Adriaan
A
Smook
Marjan
M
van de Gaar
Marie José
MJ
Heeringa
Peter
P
de Winther
Menno P J
MP
Tervaert
Jan Willem Cohen
JW
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology*; D009195:Peroxidase / Q000097:blood / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics
D001057:Apolipoproteins E; D011973:Receptors, LDL; D009195:Peroxidase