Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
J. Clin. Invest. Filip K. Swirski, et al. 117:195 doi:10.1172/JCI29950 [
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Figure 5Ly-6C
hi monocytes adhere preferentially to TNF-α–activated endothelium, accumulate in lesions, and differentiate to macrophages in vivo.
(
A) Purified Ly-6C
hi monocyte phenotype after 24 hours in culture. (
B) Adherence of blood monocytes on TNF-α–treated MHECs under laminar flow conditions. Monocyte subsets were isolated from the blood of apoE
+/+ and apoE
–/– mice on chow and Western diet. (
C) Relative proportion of blood monocytes expected to adhere to activated endothelium, based on the capacity of each subset to adhere and their average abundance in peripheral blood of apoE
–/– mice on Western diet for 25 weeks. (
D) Ly-6C, F4/80, and I-A
b expression of CD45.2
+ Ly-6C
hi monocytes retrieved from aortas and spleens 24 hours after transfer into CD45.1
+ mice (both donor and recipient apoE
–/– mice consuming a Western diet). Monocytes cultured in vitro were also analyzed. (
E) F4/80 and Ly-6C coexpression on CD45.2
+ donor cells retrieved from aortas. (
F) In vivo aortic accumulation of [
111In]oxine-labeled Ly-6C
hi and Ly-6C
lo monocytes 24 hours after adoptive transfer in apoE
–/– mice on Western diet. (
G) Phosphorimager plates depicting relative distribution of signal in aortas of apoE
–/– mice that received equal numbers of Ly-6C
hi apoE
–/– or Ly-6C
lo apoE
–/– monocytes. (
H) Relative proportion of Ly-6C
hi and Ly-6C
lo monocytes expected to accumulate in atherosclerotic aortas, based on the capacity of each subset for aortic accumulation and their average abundance in peripheral blood of apoE
–/– mice on Western diet for 25 weeks. Shown are 1 of 2–3 independent experiments. Student’s
t test was used.