Dendritic cells pulsed with malondialdehyde modified low density lipoprotein aggravate atherosclerosis in Apoe(-/-) mice.
OBJECTIVE
Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to modified lipoproteins. Dendritic cells (DCs), which are professional antigen-presenting cells that activate T cells, are present in atherosclerotic lesions but their role for atherosclerosis-related immunity is unclear.


RESULTS
To evaluate the role of DC in atherosclerosis, DCs pulsed with malondialdehyde modified low density lipoprotein (MDA-LDL) were transferred into Apoe(-/-) mice. The extent of disease was measured in the aortic root and was compared to that in animals treated with Keyhole Limpet Hemocyanin (KLH) pulsed DCs and to untreated animals. Mice receiving MDA-LDL pulsed DCs showed significantly larger atherosclerotic lesions compared to controls, with increased inflammation in the lesions and antigen-specific immune responses. Furthermore, MDA-LDL administration in complete Freund's adjuvant, which is atheroprotective, led to the induction of regulatory T cells whereas MDA-LDL-DCs treatment did not, suggesting that modulation of immune properties can result in different effects on atherosclerosis.


CONCLUSIONS
DCs presenting components of LDL promote specific immunity to their antigen, increase lesion inflammation and accelerate atherosclerosis.
Hjerpe
Charlotta
C
Centre for Molecular Medicine and Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Johansson
Daniel
D
Hermansson
Andreas
A
Hansson
Göran K
GK
Zhou
Xinghua
X
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D005260:Female; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008315:Malondialdehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C502964:malondialdehyde-low density lipoprotein, mouse; D008315:Malondialdehyde