Lactoferrin acts on I-A and I-E/C antigen subpopulations of mouse peritoneal macrophages in the absence of T lymphocytes and other cell types to inhibit production of granulocyte-macrophage colony stimulatory factors in vitro

Hal Broxmeyer, E. Platzer

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43 Citations (Scopus)

Abstract

The relationship between Ia antigens on mouse resident peritoneal macrophages and the ability of lactoferrin (LF) to inhibit the production of granulocyte-macrophage colony stimulatory factors (GM-CSF) from these cells was investigated. Detection of the suppressive influence of LF on release of GM-CSF from ≥ 105 macrophages/ml/plate required that the conditioned media being assessed for GM-CSF be prepared in the presence of indomethacin and/or be preincubated with anti-ferritin antiserum to respectively stop production of E-type prostaglandins and to remove acidic isoferritin-inhibitory activities that can mask the effects of LF. Treatment of mouse macrophages with monoclonal antibodies to the I-A and I-E/C subregions of Ia antigens in a complement C-dependent cytotoxicity assay killed less than 15% of the cells, but removed all Ia antigen+ macrophages and reduced GM-CSF production by ~ 50%. LF decreased GM-CSF production by untreated macrophages by ~ 50%, but had no effect on macrophages insensitive to treatment with anti-Ia plus C. Macrophages left at 37°C for 5 and 24 hr were not killed by treatment with monoclonal anti-Ia plus C and GM-CSF production by these macrophages was not suppressed by LF. Treatment of macrophages with monoclonal anti-H-2K or anti-Mac-1 plus C reduced GM-CSF production greater than 95%. Anti-I-A, -I-E/C, -H-2K, or -Mac-1, in the absence of C, had no effect on viability of macrophages or on production of GM-CSF, but anti-I-A and -I-E/C each blocked the inhibitory action of LF. Lower concentration of these antibodies could block the action of LF when anti-I-A and anti-I-E/C were mixed together better than when they were each used separately. The removal of Thy-1.2+ cells from unseparated or adherent peritoneal cells resulted in populations of cells that were up to 100% positive for nonspecific esterase, and did not influence GM-CSF production from these cells, the reduction of GM-CSF from these cells by LF, or the reduction of GM-CSF by the removal of Ia antigen+ cells. The results were similar whether or not T cells were removed from the assay marrow by treatment with antibodies Ly-1.1, Ly-2.2, and Qa4 plus C. These studies suggest that LF inhibits the production of GM-CSF from an Ia antigen+ subpopulation of mouse peritoneal macrophages in the absence of T lymphocytes and other cell types such as fibroblasts and endothelial cells. These interactions may be of relevance to the regulation of myelopoiesis.

Original languageEnglish
Pages (from-to)306-314
Number of pages9
JournalJournal of Immunology
Volume133
Issue number1
StatePublished - 1984

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Lactoferrin
Peritoneal Macrophages
Granulocytes
Macrophages
T-Lymphocytes
Histocompatibility Antigens Class II
I-E-antigen
In Vitro Techniques
Myelopoiesis

ASJC Scopus subject areas

  • Immunology

Cite this

@article{e8fd143607514f5cae2e0ac150aa283c,
title = "Lactoferrin acts on I-A and I-E/C antigen subpopulations of mouse peritoneal macrophages in the absence of T lymphocytes and other cell types to inhibit production of granulocyte-macrophage colony stimulatory factors in vitro",
abstract = "The relationship between Ia antigens on mouse resident peritoneal macrophages and the ability of lactoferrin (LF) to inhibit the production of granulocyte-macrophage colony stimulatory factors (GM-CSF) from these cells was investigated. Detection of the suppressive influence of LF on release of GM-CSF from ≥ 105 macrophages/ml/plate required that the conditioned media being assessed for GM-CSF be prepared in the presence of indomethacin and/or be preincubated with anti-ferritin antiserum to respectively stop production of E-type prostaglandins and to remove acidic isoferritin-inhibitory activities that can mask the effects of LF. Treatment of mouse macrophages with monoclonal antibodies to the I-A and I-E/C subregions of Ia antigens in a complement C-dependent cytotoxicity assay killed less than 15{\%} of the cells, but removed all Ia antigen+ macrophages and reduced GM-CSF production by ~ 50{\%}. LF decreased GM-CSF production by untreated macrophages by ~ 50{\%}, but had no effect on macrophages insensitive to treatment with anti-Ia plus C. Macrophages left at 37°C for 5 and 24 hr were not killed by treatment with monoclonal anti-Ia plus C and GM-CSF production by these macrophages was not suppressed by LF. Treatment of macrophages with monoclonal anti-H-2K or anti-Mac-1 plus C reduced GM-CSF production greater than 95{\%}. Anti-I-A, -I-E/C, -H-2K, or -Mac-1, in the absence of C, had no effect on viability of macrophages or on production of GM-CSF, but anti-I-A and -I-E/C each blocked the inhibitory action of LF. Lower concentration of these antibodies could block the action of LF when anti-I-A and anti-I-E/C were mixed together better than when they were each used separately. The removal of Thy-1.2+ cells from unseparated or adherent peritoneal cells resulted in populations of cells that were up to 100{\%} positive for nonspecific esterase, and did not influence GM-CSF production from these cells, the reduction of GM-CSF from these cells by LF, or the reduction of GM-CSF by the removal of Ia antigen+ cells. The results were similar whether or not T cells were removed from the assay marrow by treatment with antibodies Ly-1.1, Ly-2.2, and Qa4 plus C. These studies suggest that LF inhibits the production of GM-CSF from an Ia antigen+ subpopulation of mouse peritoneal macrophages in the absence of T lymphocytes and other cell types such as fibroblasts and endothelial cells. These interactions may be of relevance to the regulation of myelopoiesis.",
author = "Hal Broxmeyer and E. Platzer",
year = "1984",
language = "English",
volume = "133",
pages = "306--314",
journal = "Journal of Immunology",
issn = "0022-1767",
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T1 - Lactoferrin acts on I-A and I-E/C antigen subpopulations of mouse peritoneal macrophages in the absence of T lymphocytes and other cell types to inhibit production of granulocyte-macrophage colony stimulatory factors in vitro

AU - Broxmeyer, Hal

AU - Platzer, E.

PY - 1984

Y1 - 1984

N2 - The relationship between Ia antigens on mouse resident peritoneal macrophages and the ability of lactoferrin (LF) to inhibit the production of granulocyte-macrophage colony stimulatory factors (GM-CSF) from these cells was investigated. Detection of the suppressive influence of LF on release of GM-CSF from ≥ 105 macrophages/ml/plate required that the conditioned media being assessed for GM-CSF be prepared in the presence of indomethacin and/or be preincubated with anti-ferritin antiserum to respectively stop production of E-type prostaglandins and to remove acidic isoferritin-inhibitory activities that can mask the effects of LF. Treatment of mouse macrophages with monoclonal antibodies to the I-A and I-E/C subregions of Ia antigens in a complement C-dependent cytotoxicity assay killed less than 15% of the cells, but removed all Ia antigen+ macrophages and reduced GM-CSF production by ~ 50%. LF decreased GM-CSF production by untreated macrophages by ~ 50%, but had no effect on macrophages insensitive to treatment with anti-Ia plus C. Macrophages left at 37°C for 5 and 24 hr were not killed by treatment with monoclonal anti-Ia plus C and GM-CSF production by these macrophages was not suppressed by LF. Treatment of macrophages with monoclonal anti-H-2K or anti-Mac-1 plus C reduced GM-CSF production greater than 95%. Anti-I-A, -I-E/C, -H-2K, or -Mac-1, in the absence of C, had no effect on viability of macrophages or on production of GM-CSF, but anti-I-A and -I-E/C each blocked the inhibitory action of LF. Lower concentration of these antibodies could block the action of LF when anti-I-A and anti-I-E/C were mixed together better than when they were each used separately. The removal of Thy-1.2+ cells from unseparated or adherent peritoneal cells resulted in populations of cells that were up to 100% positive for nonspecific esterase, and did not influence GM-CSF production from these cells, the reduction of GM-CSF from these cells by LF, or the reduction of GM-CSF by the removal of Ia antigen+ cells. The results were similar whether or not T cells were removed from the assay marrow by treatment with antibodies Ly-1.1, Ly-2.2, and Qa4 plus C. These studies suggest that LF inhibits the production of GM-CSF from an Ia antigen+ subpopulation of mouse peritoneal macrophages in the absence of T lymphocytes and other cell types such as fibroblasts and endothelial cells. These interactions may be of relevance to the regulation of myelopoiesis.

AB - The relationship between Ia antigens on mouse resident peritoneal macrophages and the ability of lactoferrin (LF) to inhibit the production of granulocyte-macrophage colony stimulatory factors (GM-CSF) from these cells was investigated. Detection of the suppressive influence of LF on release of GM-CSF from ≥ 105 macrophages/ml/plate required that the conditioned media being assessed for GM-CSF be prepared in the presence of indomethacin and/or be preincubated with anti-ferritin antiserum to respectively stop production of E-type prostaglandins and to remove acidic isoferritin-inhibitory activities that can mask the effects of LF. Treatment of mouse macrophages with monoclonal antibodies to the I-A and I-E/C subregions of Ia antigens in a complement C-dependent cytotoxicity assay killed less than 15% of the cells, but removed all Ia antigen+ macrophages and reduced GM-CSF production by ~ 50%. LF decreased GM-CSF production by untreated macrophages by ~ 50%, but had no effect on macrophages insensitive to treatment with anti-Ia plus C. Macrophages left at 37°C for 5 and 24 hr were not killed by treatment with monoclonal anti-Ia plus C and GM-CSF production by these macrophages was not suppressed by LF. Treatment of macrophages with monoclonal anti-H-2K or anti-Mac-1 plus C reduced GM-CSF production greater than 95%. Anti-I-A, -I-E/C, -H-2K, or -Mac-1, in the absence of C, had no effect on viability of macrophages or on production of GM-CSF, but anti-I-A and -I-E/C each blocked the inhibitory action of LF. Lower concentration of these antibodies could block the action of LF when anti-I-A and anti-I-E/C were mixed together better than when they were each used separately. The removal of Thy-1.2+ cells from unseparated or adherent peritoneal cells resulted in populations of cells that were up to 100% positive for nonspecific esterase, and did not influence GM-CSF production from these cells, the reduction of GM-CSF from these cells by LF, or the reduction of GM-CSF by the removal of Ia antigen+ cells. The results were similar whether or not T cells were removed from the assay marrow by treatment with antibodies Ly-1.1, Ly-2.2, and Qa4 plus C. These studies suggest that LF inhibits the production of GM-CSF from an Ia antigen+ subpopulation of mouse peritoneal macrophages in the absence of T lymphocytes and other cell types such as fibroblasts and endothelial cells. These interactions may be of relevance to the regulation of myelopoiesis.

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