Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells.

Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells. Abstract Text:

Dongying Cui,Edward Thorp,Yankun Li,Nan Wang,Laurent Yvan-Charvet,Alan R Tall,Ira Tabas,Dongying Cui,Edward Thorp,Yankun Li,Nan Wang,Laurent Yvan-Charvet,Alan R Tall,Ira Tabas,

One of the most important functions of macrophages is the phagocytosis of apoptotic cells (ACs). ACs deliver large amounts membrane-derived cholesterol to phagocytes, which, if not handled properly, can be cytotoxic. In atherosclerosis, where the ACs are cholesterol-loaded, this situation is exaggerated, because the ACs deliver both endogenous membrane cholesterol and stored lipoprotein-derived cholesterol. To examine how phagocytes handle this very large amount of cholesterol, we incubated macrophage phagocytes with cholesterol-loaded ACs. Our results show that the phagocytes call into play a number of cellular responses to protect them from cholesterol-induced cytotoxicity. First, through efficient trafficking of the internalized AC-derived cholesterol to acyl-CoA:cholesterol acyltransferase (ACAT) in the endoplasmic reticulum, phagocytes efficiently esterify the cholesterol and thus prevent its toxic effects. However, the phagocytes show no signs of cytotoxicity even when ACAT is rendered dysfunctional, as might occur in advanced atherosclerotic lesions. Under these conditions, the phagocytes remain viable through massive efflux of AC-derived cholesterol. Remarkably, these phagocytes still show a survival response even when high cholesterol levels are maintained in the post-phagocytosis period by subsequent incubation with atherogenic lipoproteins, as also may occur in atheromata. In this case, death in phagocytes is prevented by activation of survival pathways involving PI-3 kinase/Akt and NF-kappaB. Thus, macrophages that have ingested ACs successfully employ three survival mechanisms -- cholesterol esterification, massive cholesterol efflux, and cell-survival signaling. These findings have implications for macrophage physiology in both AC clearance and atherosclerotic plaque progression.

Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells. Publishing Authors By Initials

D Cui,E Thorp,Y Li,N Wang,L Yvan-Charvet,AR Tall,I Tabas,D Cui,E Thorp,Y Li,N Wang,L Yvan-Charvet,AR Tall,I Tabas,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of leukocyte biology

VOLUME: 82

Page Numbers: 1040-50

Journal Abbreviation: J. Leukoc. Biol.

ISSN: 0741-5400

DAY: 18

MONTH: 06

YEAR: 2007

Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8405628

Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells.

AFFILIATION: Department of Medicine, Columbia University, New York, NY 10032, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL75662

ACRONYM: HL

MEDLINETA: J Leukoc Biol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells Related Publications

• A perspective on the role of collagenase in recessive dystrophic epidermolysis bullosa.
• Acid sphingomyelinase promotes lipoprotein retention within early atheromata and accelerates lesion progression.
• Apoptosis and efferocytosis in mouse models of atherosclerosis.
• Macrophages, apoptotic cells and cholesterol -- strategies for survival: an interview with Dr. Ira Tabas. Interview by Helene F. Rosenberg.
• Mertk receptor mutation reduces efferocytosis efficiency and promotes apoptotic cell accumulation and plaque necrosis in atherosclerotic lesions of apoe-/- mice.
• Pioglitazone increases macrophage apoptosis and plaque necrosis in advanced atherosclerotic lesions of nondiabetic low-density lipoprotein receptor-null mice.
• Pivotal advance: macrophages become resistant to cholesterol-induced death after phagocytosis of apoptotic cells.
• Signal transducer and activator of transcription-1 is critical for apoptosis in macrophages subjected to endoplasmic reticulum stress in vitro and in advanced atherosclerotic lesions in vivo.
• The inflammatory cytokine response of cholesterol-enriched macrophages is dampened by stimulated pinocytosis.
• Videos in clinical medicine. Placement of a femoral venous catheter.