Native low-density lipoprotein uptake by macrophage colony-stimulating factor-differentiated human macrophages is mediated by macropinocytosis and micropinocytosis.

Arteriosclerosis, Thrombosis, and Vascular Biology
Joshua J AnzingerH S Kruth

Abstract

To examine the pinocytotic pathways mediating native low-density lipoprotein (LDL) uptake by human macrophage colony-stimulating factor-differentiated macrophages (the predominant macrophage phenotype in human atherosclerotic plaques). We identified the kinase inhibitor SU6656 and the Rho GTPase inhibitor toxin B as inhibitors of macrophage fluid-phase pinocytosis of LDL. Assessment of macropinocytosis by time-lapse microscopy revealed that both drugs almost completely inhibited macropinocytosis, although LDL uptake and cholesterol accumulation by macrophages were only partially inhibited (approximately 40%) by these agents. Therefore, we investigated the role of micropinocytosis in mediating LDL uptake in macrophages and identified bafilomycin A1 as an additional partial inhibitor (approximately 40%) of macrophage LDL uptake that targeted micropinocytosis. When macrophages were incubated with both bafilomycin A1 and SU6656, inhibition of LDL uptake was additive (reaching 80%), showing that these inhibitors target different pathways. Microscopic analysis of fluid-phase uptake pathways in these macrophages confirmed that LDL uptake occurs through both macropinocytosis and micropinocytosis. Our findings show that human macrophage...Continue Reading

References

Jan 16, 1976·Science·M S Brown, J L Goldstein
Dec 29, 1978·Biochemical and Biophysical Research Communications·H F HoffA M Gotto
Mar 1, 1976·The Journal of Cell Biology·R M SteinmanZ A Cohn
Feb 21, 1992·Cell·K G RothbergR G Anderson
Nov 1, 1989·The Journal of Experimental Medicine·E L Racoosin, J A Swanson
Jan 1, 1983·Methods in Enzymology·J L GoldsteinM S Brown
Feb 1, 1995·Journal of Leukocyte Biology·A Bidani, T A Heming
Aug 1, 1996·The Journal of Cell Biology·H RadhakrishnaJ G Donaldson
May 23, 1997·The Journal of Biological Chemistry·J F PresleyF R Maxfield
Jan 14, 1999·The New England Journal of Medicine·R Ross
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·A SubtilT E McGraw
Nov 14, 2000·Molecular and Cellular Biology·R A BlakeS A Courtneidge
Jul 26, 2002·International Journal of Hematology·Kiyoko S Akagawa
Mar 7, 2003·Nature·Sean D Conner, Sandra L Schmid
Apr 3, 2003·European Journal of Immunology·Wenyan GuoReem Al-Daccak
Nov 1, 1995·Trends in Cell Biology·J A Swanson, C Watts
May 18, 2004·Molecular Biology of the Cell·Naava NaslavskyJulie G Donaldson
Jan 18, 2006·Nature Cell Biology·Andrés Hurtado-LorenzoVladimir Marshansky
Dec 13, 2006·FEMS Microbiology Letters·Daniel J-F ChinnapenWayne I Lencer
Dec 15, 2006·Journal of Cellular Physiology·Kousuke KasaharaNaoto Yamaguchi
Sep 14, 2007·The Biochemical Journal·Jenny BainPhilip Cohen
Mar 7, 2008·The American Journal of Pathology·Stephen W WaldoHoward S Kruth
Oct 30, 2008·Journal of Lipid Research·Paul A VanderLaanGodfrey S Getz
Nov 18, 2008·Journal of Lipid Research·Daniel Steinberg
Mar 26, 2009·Annual Review of Biochemistry·Gary J Doherty, Harvey T McMahon
May 19, 2009·The Journal of Experimental Biology·Dennis BrownVladimir Marshansky

❮ Previous
Next ❯

Citations

Feb 22, 2012·Cardiovascular Research·Sima AllahverdianGordon A Francis
Sep 12, 2012·Current Opinion in Lipidology·Karina Di Gregoli, Jason L Johnson
Jun 17, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Klaus LeyCatherine C Hedrick
Aug 14, 2012·The Journal of Clinical Investigation·Ekaterina K KoltsovaKlaus Ley
Apr 13, 2013·Lipids in Health and Disease·Pauli Ohukainen
Jul 27, 2012·Journal of Lipid Research·Jason M MeyerDeneys R van der Westhuyzen
Dec 18, 2015·Thrombosis and Haemostasis·Annas Al-ShareaAndrew J Murphy
Aug 16, 2016·The Journal of Clinical Investigation·Takuro MiyazakiAkira Miyazaki
Aug 5, 2016·Antioxidants & Redox Signaling·Pushpankur GhoshalGábor Csányi
Jan 16, 2013·Journal of Dental Research·M MorishitaT Nishihara
Jun 16, 2017·Journal of Vascular Research·Joshua J AnzingerHoward S Kruth
Jul 30, 2016·Journal of Applied Physiology·Toshihiro ImamuraGabriel G Haddad
Jun 2, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Xueting JinHoward S Kruth
Oct 1, 2011·Circulation Research·Malin C LevinJan Borén
Mar 29, 2018·Current Medicinal Chemistry·Takuro Miyazaki, Akira Miyazaki
Aug 7, 2020·Membranes·Xiao Peng LinPaul A Gleeson
May 11, 2018·Current Opinion in Lipidology·Alexander N Orekhov
Apr 11, 2019·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Sasha A DoodnauthMichelle E Maxson
Apr 23, 2017·Cellular and Molecular Life Sciences : CMLS·Takuro Miyazaki, Akira Miyazaki
Nov 5, 2019·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Diego LuceroAlan T Remaley
Sep 18, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Ming-Zhu XiaoYuan-Yuan Cheng
Jul 19, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Richard J LightbodyAnnette Graham

❮ Previous
Next ❯

Related Concepts

Related Feeds

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.