Role of Low-Affinity Fc Receptors in Antibody-dependent Tumor Cell Phagocytosis by Human Monocyte-derived Macrophages

David H Munn, Mary McBride, Nai Kong V. Cheung

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Human monocyte-derived macrophages (MDM) mediate efficient an tibody-dependent cellular cytotoxicity (ADCC) against a variety of human tumor cell types in the presence of an anti-tumor monoclonal antibody. We have recently shown that the mechanism of this ADCC in our in vitro system involves phagocytosis of intact tumor cells. Some forms of macrophage ADCC have been reported to be inhibited by serum iininiinoglobulin, which competes with monoclonal antibodies for binding to the high-affinity Fc receptor (FcRI). In this study we investigated the role of the three macrophage FcR-7 in antibody-dependent tumor cell phagocytosis. Hybridoma cells bearing surface antibody directed against either of the two low-affinity Fc receptors (FcRII or FcRIII) were efficiently phagocytosed by MDM. compared to hybridomas bearing irrelevant antibody. Soluble anti-receptor antibodies against FcRII and FcRIII were able to inhibit ADCC but only when both antibodies were simultaneously present. These data suggest that either low-affinity Fc receptor is capable of functioning independently to mediate phagocytosis of tumor cells. Consistent with a mechanism involving the low-affinity receptors rather than FcRI, antibody-dependent phagocytosis occurred in the presence of human serum, purified human IgG, and irrelevant murine antibody. Greater than 75% of the MDM in our culture system were able to ingest tumor cells when a suitable target was available. Optimal phagocytosis occurred at monoclonal antibody concentrations of 10-100 ng/ml. Like other forms of macrophage phagocytosis, ingestion of tumor cells required the presence of divalent cations (either Ca2* or Mg2*) and an intact actin cytoskeleton (as indicated by sensitivity to cytochalasin D). Because FcRI is normally occupied in vivo by serum immunoglobulin, the participation of low-affinity FcR in tumor cell phagocytosis is potentially important in establishing the in vivo applica bility of this efficient form of cytotoxicity.

Original languageEnglish (US)
Pages (from-to)1117-1123
Number of pages7
JournalCancer Research
Volume51
Issue number4
StatePublished - Jan 1 1991

Fingerprint

Neoplasm Antibodies
Cytophagocytosis
Fc Receptors
Phagocytosis
Macrophages
Antibodies
Neoplasms
Monoclonal Antibodies
Hybridomas
Serum
Cytochalasin D
Divalent Cations
Actin Cytoskeleton
Immunoglobulins
Anti-Idiotypic Antibodies
Eating
Immunoglobulin G

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Role of Low-Affinity Fc Receptors in Antibody-dependent Tumor Cell Phagocytosis by Human Monocyte-derived Macrophages. / Munn, David H; McBride, Mary; Cheung, Nai Kong V.

In: Cancer Research, Vol. 51, No. 4, 01.01.1991, p. 1117-1123.

Research output: Contribution to journalArticle

@article{eb5ec31bfca3483fb50ab48eefab3791,
title = "Role of Low-Affinity Fc Receptors in Antibody-dependent Tumor Cell Phagocytosis by Human Monocyte-derived Macrophages",
abstract = "Human monocyte-derived macrophages (MDM) mediate efficient an tibody-dependent cellular cytotoxicity (ADCC) against a variety of human tumor cell types in the presence of an anti-tumor monoclonal antibody. We have recently shown that the mechanism of this ADCC in our in vitro system involves phagocytosis of intact tumor cells. Some forms of macrophage ADCC have been reported to be inhibited by serum iininiinoglobulin, which competes with monoclonal antibodies for binding to the high-affinity Fc receptor (FcRI). In this study we investigated the role of the three macrophage FcR-7 in antibody-dependent tumor cell phagocytosis. Hybridoma cells bearing surface antibody directed against either of the two low-affinity Fc receptors (FcRII or FcRIII) were efficiently phagocytosed by MDM. compared to hybridomas bearing irrelevant antibody. Soluble anti-receptor antibodies against FcRII and FcRIII were able to inhibit ADCC but only when both antibodies were simultaneously present. These data suggest that either low-affinity Fc receptor is capable of functioning independently to mediate phagocytosis of tumor cells. Consistent with a mechanism involving the low-affinity receptors rather than FcRI, antibody-dependent phagocytosis occurred in the presence of human serum, purified human IgG, and irrelevant murine antibody. Greater than 75{\%} of the MDM in our culture system were able to ingest tumor cells when a suitable target was available. Optimal phagocytosis occurred at monoclonal antibody concentrations of 10-100 ng/ml. Like other forms of macrophage phagocytosis, ingestion of tumor cells required the presence of divalent cations (either Ca2* or Mg2*) and an intact actin cytoskeleton (as indicated by sensitivity to cytochalasin D). Because FcRI is normally occupied in vivo by serum immunoglobulin, the participation of low-affinity FcR in tumor cell phagocytosis is potentially important in establishing the in vivo applica bility of this efficient form of cytotoxicity.",
author = "Munn, {David H} and Mary McBride and Cheung, {Nai Kong V.}",
year = "1991",
month = "1",
day = "1",
language = "English (US)",
volume = "51",
pages = "1117--1123",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Role of Low-Affinity Fc Receptors in Antibody-dependent Tumor Cell Phagocytosis by Human Monocyte-derived Macrophages

AU - Munn, David H

AU - McBride, Mary

AU - Cheung, Nai Kong V.

PY - 1991/1/1

Y1 - 1991/1/1

N2 - Human monocyte-derived macrophages (MDM) mediate efficient an tibody-dependent cellular cytotoxicity (ADCC) against a variety of human tumor cell types in the presence of an anti-tumor monoclonal antibody. We have recently shown that the mechanism of this ADCC in our in vitro system involves phagocytosis of intact tumor cells. Some forms of macrophage ADCC have been reported to be inhibited by serum iininiinoglobulin, which competes with monoclonal antibodies for binding to the high-affinity Fc receptor (FcRI). In this study we investigated the role of the three macrophage FcR-7 in antibody-dependent tumor cell phagocytosis. Hybridoma cells bearing surface antibody directed against either of the two low-affinity Fc receptors (FcRII or FcRIII) were efficiently phagocytosed by MDM. compared to hybridomas bearing irrelevant antibody. Soluble anti-receptor antibodies against FcRII and FcRIII were able to inhibit ADCC but only when both antibodies were simultaneously present. These data suggest that either low-affinity Fc receptor is capable of functioning independently to mediate phagocytosis of tumor cells. Consistent with a mechanism involving the low-affinity receptors rather than FcRI, antibody-dependent phagocytosis occurred in the presence of human serum, purified human IgG, and irrelevant murine antibody. Greater than 75% of the MDM in our culture system were able to ingest tumor cells when a suitable target was available. Optimal phagocytosis occurred at monoclonal antibody concentrations of 10-100 ng/ml. Like other forms of macrophage phagocytosis, ingestion of tumor cells required the presence of divalent cations (either Ca2* or Mg2*) and an intact actin cytoskeleton (as indicated by sensitivity to cytochalasin D). Because FcRI is normally occupied in vivo by serum immunoglobulin, the participation of low-affinity FcR in tumor cell phagocytosis is potentially important in establishing the in vivo applica bility of this efficient form of cytotoxicity.

AB - Human monocyte-derived macrophages (MDM) mediate efficient an tibody-dependent cellular cytotoxicity (ADCC) against a variety of human tumor cell types in the presence of an anti-tumor monoclonal antibody. We have recently shown that the mechanism of this ADCC in our in vitro system involves phagocytosis of intact tumor cells. Some forms of macrophage ADCC have been reported to be inhibited by serum iininiinoglobulin, which competes with monoclonal antibodies for binding to the high-affinity Fc receptor (FcRI). In this study we investigated the role of the three macrophage FcR-7 in antibody-dependent tumor cell phagocytosis. Hybridoma cells bearing surface antibody directed against either of the two low-affinity Fc receptors (FcRII or FcRIII) were efficiently phagocytosed by MDM. compared to hybridomas bearing irrelevant antibody. Soluble anti-receptor antibodies against FcRII and FcRIII were able to inhibit ADCC but only when both antibodies were simultaneously present. These data suggest that either low-affinity Fc receptor is capable of functioning independently to mediate phagocytosis of tumor cells. Consistent with a mechanism involving the low-affinity receptors rather than FcRI, antibody-dependent phagocytosis occurred in the presence of human serum, purified human IgG, and irrelevant murine antibody. Greater than 75% of the MDM in our culture system were able to ingest tumor cells when a suitable target was available. Optimal phagocytosis occurred at monoclonal antibody concentrations of 10-100 ng/ml. Like other forms of macrophage phagocytosis, ingestion of tumor cells required the presence of divalent cations (either Ca2* or Mg2*) and an intact actin cytoskeleton (as indicated by sensitivity to cytochalasin D). Because FcRI is normally occupied in vivo by serum immunoglobulin, the participation of low-affinity FcR in tumor cell phagocytosis is potentially important in establishing the in vivo applica bility of this efficient form of cytotoxicity.

UR - http://www.scopus.com/inward/record.url?scp=0025802963&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025802963&partnerID=8YFLogxK

M3 - Article

C2 - 1825476

AN - SCOPUS:0025802963

VL - 51

SP - 1117

EP - 1123

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 4

ER -