The effect of ethanol on asialoglycoprotein receptor-mediated phagocytosis of apoptotic cells by rat hepatocytes

Benita L McVicker, Dean J. Tuma, Jacy A. Kubik, Agnes M. Hindemith, Cheryl R. Baldwin, Carol A Casey

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Apoptotic cell death is a well-defined process that is controlled by intrinsic cellular mechanisms followed by the generation of apoptotic bodies and their subsequent rapid elimination through the action of phagocytic cells. Within the liver, the asialoglycoprotein receptor (ASGP-R) has been shown to be involved in the phagocytosis of apoptotic hepatocytes, as well as altered cellular endocytic events after ethanol administration. The goal of the present study was to further clarify the capacity of ASGP-R to phagocytose apoptotic cells in relationship to the damaging events that occur with alcohol consumption. For these experiments, we used an in vitro suspension assay coupled with flow cytometry to measure apoptotic cell engulfment by rat hepatocytes after chronic ethanol administration. The results of this assay indicated that the phagocytosis of apoptotic cells was decreased significandy (30% to 42%, P < .05) in the presence of antibody specific for ASGP-R as well as the introduction of competing sugars in the media. In addition, uptake of apoptotic cells was impaired by 40% to 60% (P < .05) in cells obtained from ethanol-fed animals as compared with controls. In conclusion, the ASGP-R is involved in the recognition and uptake of apoptotic cells and this process is altered significantly by ethanol treatment. These findings may play a role in a better understanding of the clinical manifestations of alcohol-induced liver injury as altered uptake of apoptotic cells via ASGP-R may result in the release of proinflammatory mediators, the introduction of autoimmune responses, and inflammatory injury to the tissue.

Original languageEnglish (US)
Pages (from-to)1478-1487
Number of pages10
JournalHepatology
Volume36
Issue number6
DOIs
StatePublished - Dec 1 2002

Fingerprint

Asialoglycoprotein Receptor
Cytophagocytosis
Hepatocytes
Ethanol
Liver
Wounds and Injuries
Phagocytes
Autoimmunity
Phagocytosis
Alcohol Drinking
Suspensions
Flow Cytometry
Cell Death
Alcohols
Antibodies

ASJC Scopus subject areas

  • Hepatology

Cite this

The effect of ethanol on asialoglycoprotein receptor-mediated phagocytosis of apoptotic cells by rat hepatocytes. / McVicker, Benita L; Tuma, Dean J.; Kubik, Jacy A.; Hindemith, Agnes M.; Baldwin, Cheryl R.; Casey, Carol A.

In: Hepatology, Vol. 36, No. 6, 01.12.2002, p. 1478-1487.

Research output: Contribution to journalArticle

McVicker, Benita L ; Tuma, Dean J. ; Kubik, Jacy A. ; Hindemith, Agnes M. ; Baldwin, Cheryl R. ; Casey, Carol A. / The effect of ethanol on asialoglycoprotein receptor-mediated phagocytosis of apoptotic cells by rat hepatocytes. In: Hepatology. 2002 ; Vol. 36, No. 6. pp. 1478-1487.
@article{39103911d19c4fa3a78c0ce556601f64,
title = "The effect of ethanol on asialoglycoprotein receptor-mediated phagocytosis of apoptotic cells by rat hepatocytes",
abstract = "Apoptotic cell death is a well-defined process that is controlled by intrinsic cellular mechanisms followed by the generation of apoptotic bodies and their subsequent rapid elimination through the action of phagocytic cells. Within the liver, the asialoglycoprotein receptor (ASGP-R) has been shown to be involved in the phagocytosis of apoptotic hepatocytes, as well as altered cellular endocytic events after ethanol administration. The goal of the present study was to further clarify the capacity of ASGP-R to phagocytose apoptotic cells in relationship to the damaging events that occur with alcohol consumption. For these experiments, we used an in vitro suspension assay coupled with flow cytometry to measure apoptotic cell engulfment by rat hepatocytes after chronic ethanol administration. The results of this assay indicated that the phagocytosis of apoptotic cells was decreased significandy (30{\%} to 42{\%}, P < .05) in the presence of antibody specific for ASGP-R as well as the introduction of competing sugars in the media. In addition, uptake of apoptotic cells was impaired by 40{\%} to 60{\%} (P < .05) in cells obtained from ethanol-fed animals as compared with controls. In conclusion, the ASGP-R is involved in the recognition and uptake of apoptotic cells and this process is altered significantly by ethanol treatment. These findings may play a role in a better understanding of the clinical manifestations of alcohol-induced liver injury as altered uptake of apoptotic cells via ASGP-R may result in the release of proinflammatory mediators, the introduction of autoimmune responses, and inflammatory injury to the tissue.",
author = "McVicker, {Benita L} and Tuma, {Dean J.} and Kubik, {Jacy A.} and Hindemith, {Agnes M.} and Baldwin, {Cheryl R.} and Casey, {Carol A}",
year = "2002",
month = "12",
day = "1",
doi = "10.1053/jhep.2002.37137",
language = "English (US)",
volume = "36",
pages = "1478--1487",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - The effect of ethanol on asialoglycoprotein receptor-mediated phagocytosis of apoptotic cells by rat hepatocytes

AU - McVicker, Benita L

AU - Tuma, Dean J.

AU - Kubik, Jacy A.

AU - Hindemith, Agnes M.

AU - Baldwin, Cheryl R.

AU - Casey, Carol A

PY - 2002/12/1

Y1 - 2002/12/1

N2 - Apoptotic cell death is a well-defined process that is controlled by intrinsic cellular mechanisms followed by the generation of apoptotic bodies and their subsequent rapid elimination through the action of phagocytic cells. Within the liver, the asialoglycoprotein receptor (ASGP-R) has been shown to be involved in the phagocytosis of apoptotic hepatocytes, as well as altered cellular endocytic events after ethanol administration. The goal of the present study was to further clarify the capacity of ASGP-R to phagocytose apoptotic cells in relationship to the damaging events that occur with alcohol consumption. For these experiments, we used an in vitro suspension assay coupled with flow cytometry to measure apoptotic cell engulfment by rat hepatocytes after chronic ethanol administration. The results of this assay indicated that the phagocytosis of apoptotic cells was decreased significandy (30% to 42%, P < .05) in the presence of antibody specific for ASGP-R as well as the introduction of competing sugars in the media. In addition, uptake of apoptotic cells was impaired by 40% to 60% (P < .05) in cells obtained from ethanol-fed animals as compared with controls. In conclusion, the ASGP-R is involved in the recognition and uptake of apoptotic cells and this process is altered significantly by ethanol treatment. These findings may play a role in a better understanding of the clinical manifestations of alcohol-induced liver injury as altered uptake of apoptotic cells via ASGP-R may result in the release of proinflammatory mediators, the introduction of autoimmune responses, and inflammatory injury to the tissue.

AB - Apoptotic cell death is a well-defined process that is controlled by intrinsic cellular mechanisms followed by the generation of apoptotic bodies and their subsequent rapid elimination through the action of phagocytic cells. Within the liver, the asialoglycoprotein receptor (ASGP-R) has been shown to be involved in the phagocytosis of apoptotic hepatocytes, as well as altered cellular endocytic events after ethanol administration. The goal of the present study was to further clarify the capacity of ASGP-R to phagocytose apoptotic cells in relationship to the damaging events that occur with alcohol consumption. For these experiments, we used an in vitro suspension assay coupled with flow cytometry to measure apoptotic cell engulfment by rat hepatocytes after chronic ethanol administration. The results of this assay indicated that the phagocytosis of apoptotic cells was decreased significandy (30% to 42%, P < .05) in the presence of antibody specific for ASGP-R as well as the introduction of competing sugars in the media. In addition, uptake of apoptotic cells was impaired by 40% to 60% (P < .05) in cells obtained from ethanol-fed animals as compared with controls. In conclusion, the ASGP-R is involved in the recognition and uptake of apoptotic cells and this process is altered significantly by ethanol treatment. These findings may play a role in a better understanding of the clinical manifestations of alcohol-induced liver injury as altered uptake of apoptotic cells via ASGP-R may result in the release of proinflammatory mediators, the introduction of autoimmune responses, and inflammatory injury to the tissue.

UR - http://www.scopus.com/inward/record.url?scp=0036895297&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036895297&partnerID=8YFLogxK

U2 - 10.1053/jhep.2002.37137

DO - 10.1053/jhep.2002.37137

M3 - Article

C2 - 12447874

AN - SCOPUS:0036895297

VL - 36

SP - 1478

EP - 1487

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 6

ER -