Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.
Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. However, their response to hyperlipidemia remains poorly understood. Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1(low) monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1(low) monocytes at the endothelial interface and a marked accumulation of CD68(+) macrophages in several organs. Hypertriglyceridemia was accompanied by an increased expression of tissue, and plasma CCL4 and blood Gr1(low) monocyte depletion involved a pertussis-toxin-sensitive receptor axis. Collectively, these findings demonstrate that a triglyceride-rich environment can alter blood monocyte distribution, promoting the extravasation of Gr1(low) cells. The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells.
Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
Maha F
MF
Saja
Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
Lucie
L
Baudino
Renal and Vascular Inflammation Section, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
William D
WD
Jackson
Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
H Terence
HT
Cook
Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
Talat H
TH
Malik
Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
Liliane
L
Fossati-Jimack
Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
Marieta
M
Ruseva
Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK.
Matthew C
MC
Pickering
Renal and Vascular Inflammation Section, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK. Electronic address: k.woollard@imperial.ac.uk.
Kevin J
KJ
Woollard
Centre for Complement and Inflammation Research, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, Du Cane Road, London W12 ONN, UK. Electronic address: m.botto@imperial.ac.uk.
Marina
M
Botto
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D000950:Antigens, Ly; D008074:Lipoproteins; C494192:Ly-6C antigen, mouse; D014280:Triglycerides; C030087:lipoprotein triglyceride