Expansion of immunoregulatory macrophages by granulocyte-macrophage colony-stimulating factor derived from a murine mammary tumor

Yangxin Fu, Gordon Watson, Joaquin J. Jimenez, Diana M Lopez, Joaquin J Jimenez

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128 Citations (Scopus)

Abstract

Using an immunogenic nonmetastatic murine mammary adenocarcinoma (D1-DMBA-3) induced in BALB/c mice by dimethylbenzanthracene, we have previously shown that splenocytes from tumor bearers have depressed lymphocyte responses to mitogens and antigens, including tumor-associated antigens. In addition, they display decreased natural killer and T-cell cytotoxic activities. Macrophages from tumor-bearing mice appear to be responsible for the suppression of T- and B-cell responses to concanavalin A, lipopolysaccharide, and tumor-associated antigens observed in tumor bearers. The appearance of these macrophages in the spleen tightly parallels the progressive growth of the tumor and the concomitant immunosuppression. Simultaneously high levels of macrophage progenitors were observed in blood, bone marrow, lung, and liver. A significant increase of colony-stimulating activity of the granulocyte-macrophage lineage was detected in the sera from tumor-bearing mice. Higher levels of this colony-stimulating activity (CSA) were detected in tumor cystic fluid as compared with the levels in serum. A tumor cell line established in vitro from the D1-DMBA-3 in vivo tumor produces high levels of a factor with CSA in culture supernatant fluids. Partial purification of the CSA from the tumor cell line supernatants was achieved using CentriCell ultrafiltration and Sephacryl S-300 chromatography. These studies revealed that the molecular weight of the colony-stimulating-like factor is 32,000 to 35,000. The morphology of the colonies obtained in cultures using this factor is similar to that of the colonies that develop in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) but not with macrophage colony-stimulating factor (M-CSF). CSA from tumor cell supernatants was neutralized by antiserum to GM-CSF but not with anti-M-CSF or anti-granulocyte colony-stimulating factor (G-CSF). Macrophages from bone marrow or peritoneal exudates from normal mice cultured with tumor supernatant for 2 to 3 days strongly inhibit normal splenocyte responses to concanavalin A and lipopolysaccharide. The data suggest that the tumor releases a GM-CSF that alters the hemopoietic system and induces or expands macrophages, which exert a suppressive function on the immune system of tumor-bearing mice.

Original languageEnglish
Pages (from-to)227-234
Number of pages8
JournalCancer Research
Volume50
Issue number2
StatePublished - Jan 15 1990

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Granulocyte-Macrophage Colony-Stimulating Factor
Macrophages
Breast Neoplasms
Neoplasms
Colony-Stimulating Factors
9,10-Dimethyl-1,2-benzanthracene
Macrophage Colony-Stimulating Factor
Neoplasm Antigens
Concanavalin A
Tumor Cell Line
Lipopolysaccharides
Bone Marrow
Natural Killer T-Cells
Ultrafiltration
Granulocyte Colony-Stimulating Factor
Exudates and Transudates
Serum
Mitogens
Granulocytes
Immunosuppression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expansion of immunoregulatory macrophages by granulocyte-macrophage colony-stimulating factor derived from a murine mammary tumor. / Fu, Yangxin; Watson, Gordon; Jimenez, Joaquin J.; Lopez, Diana M; Jimenez, Joaquin J.

In: Cancer Research, Vol. 50, No. 2, 15.01.1990, p. 227-234.

Research output: Contribution to journalArticle

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N2 - Using an immunogenic nonmetastatic murine mammary adenocarcinoma (D1-DMBA-3) induced in BALB/c mice by dimethylbenzanthracene, we have previously shown that splenocytes from tumor bearers have depressed lymphocyte responses to mitogens and antigens, including tumor-associated antigens. In addition, they display decreased natural killer and T-cell cytotoxic activities. Macrophages from tumor-bearing mice appear to be responsible for the suppression of T- and B-cell responses to concanavalin A, lipopolysaccharide, and tumor-associated antigens observed in tumor bearers. The appearance of these macrophages in the spleen tightly parallels the progressive growth of the tumor and the concomitant immunosuppression. Simultaneously high levels of macrophage progenitors were observed in blood, bone marrow, lung, and liver. A significant increase of colony-stimulating activity of the granulocyte-macrophage lineage was detected in the sera from tumor-bearing mice. Higher levels of this colony-stimulating activity (CSA) were detected in tumor cystic fluid as compared with the levels in serum. A tumor cell line established in vitro from the D1-DMBA-3 in vivo tumor produces high levels of a factor with CSA in culture supernatant fluids. Partial purification of the CSA from the tumor cell line supernatants was achieved using CentriCell ultrafiltration and Sephacryl S-300 chromatography. These studies revealed that the molecular weight of the colony-stimulating-like factor is 32,000 to 35,000. The morphology of the colonies obtained in cultures using this factor is similar to that of the colonies that develop in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) but not with macrophage colony-stimulating factor (M-CSF). CSA from tumor cell supernatants was neutralized by antiserum to GM-CSF but not with anti-M-CSF or anti-granulocyte colony-stimulating factor (G-CSF). Macrophages from bone marrow or peritoneal exudates from normal mice cultured with tumor supernatant for 2 to 3 days strongly inhibit normal splenocyte responses to concanavalin A and lipopolysaccharide. The data suggest that the tumor releases a GM-CSF that alters the hemopoietic system and induces or expands macrophages, which exert a suppressive function on the immune system of tumor-bearing mice.

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