Very-low and low-density lipoproteins induce neutral lipid accumulation and impair migration in monocyte subsets

Scientific Reports
William D JacksonKevin J Woollard

Abstract

Blood monocytes are heterogeneous effector cells of the innate immune system. In circulation these cells are constantly in contact with lipid-rich lipoproteins, yet this interaction is poorly characterised. Our aim was to examine the functional effect of hyperlipidaemia on blood monocytes. In the Ldlr(-/-) mouse monocytes rapidly accumulate cytoplasmic neutral lipid vesicles during hyperlipidaemia. Functional analysis in vivo revealed impaired monocyte chemotaxis towards peritonitis following high fat diet due to retention of monocytes in the greater omentum. In vitro assays using human monocytes confirmed neutral lipid vesicle accumulation after exposure to LDL or VLDL. Neutral lipid accumulation did not inhibit phagocytosis, endothelial adhesion, intravascular crawling and transmigration. However, lipid loading led to a migratory defect towards C5a and disruption of cytoskeletal rearrangement, including an inhibition of RHOA signaling. These data demonstrate distinct effects of hyperlipidaemia on the chemotaxis and cytoskeletal regulation of monocyte subpopulations. These data emphasise the functional consequences of blood monocyte lipid accumulation and reveal important implications for treating inflammation, infection and a...Continue Reading

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Citations

Mar 17, 2017·Nature Reviews. Cardiology·Mohammed Shamim RahmanKevin J Woollard
Feb 17, 2018·Journal of Leukocyte Biology·Federica M Marelli-Berg, Maryam Jangani
Sep 25, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Paola M MarcovecchioCatherine C Hedrick
Aug 2, 2017·Current Opinion in Lipidology·Erik A L Biessen, Kristiaan Wouters
Jul 31, 2019·Current Opinion in Lipidology·Jaume Amengual, Tessa J Barrett
Sep 14, 2020·Immunology·Hannah Guak, Connie M Krawczyk
Mar 3, 2020·Frontiers in Cardiovascular Medicine·Jenny E KanterKarin E Bornfeldt
Apr 16, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Susanna FiorelliSonia Eligini
Jun 18, 2021·International Journal of Inflammation·Vadim GenkelIgor Shaposhnik
Sep 8, 2021·The Journal of Clinical Investigation·Masami Shimizu-AlbergineKarin E Bornfeldt

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Methods Mentioned

BETA
FACS
confocal microscopy
lavage
GTPase
GTPases

Software Mentioned

Imaris
ARRIVE
ImageJ

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