title: Deregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor in murine macrophage cell line J774A.1.
abstract: J774A.1 immortalized macrophage tumor cells display several phenotypes and functional capacities similar to that of murine peritoneal exudate macrophages (PEM). Both populations display comparable number of M-CSF receptors. Yet the number of GM-CSF receptors on J774A.1 cells is only one-fourth that of PEM (1,500 vs. 6,000 per cell). Unlike J774A.1 cells, which constitutively express c-myc transcripts, normal PEM required rMuGM-CSF for the induction of c-myc expression. Nevertheless, the growth of J774A.1 cells can be further enhanced in the presence of exogenous rMuGM-CSF, rHuM-CSF, and rMuIL-3. Treatment with either rMuIL-3 (20 ng/ml) and rHuTGF-beta 1 (1.0 ng/ml) for 24 hr at 37 degrees C, markedly enhanced the expression of GM-CSF receptors on normal PEM but not leukemic J774A.1 cells. J774A.1 cells also did not respond by autologous upregulation of GM-CSF receptors as seen in PEM following treatment with rMuGM-CSF. Treatment with either pertussis toxin (20-100 ng/ml) or H-8 (50 microM) for 24 hr led to an enhanced expression of GM-CSF receptors on J774A.1 cells in a time- and dose-dependent manner but did not result in enhanced receptor expression on normal PEM. These findings suggest that the expression of GM-CSF receptors may be regulated by mechanisms involving Gi-proteins and their downstream elements, which in turn are linked to regulatory pathways of other cytokine receptors. In J774A.1 cells, such regulatory interaction may not exist.
authors.affiliation: Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
authors.forename: K
authors.initials: K
authors.lastname: Fan
authors.forename: N
authors.initials: N
authors.lastname: Barendsen
authors.forename: L
authors.initials: L
authors.lastname: Sensenbrenner
authors.forename: B D
authors.initials: BD
authors.lastname: Chen
mesh_terms: D000818:Animals; D002455:Cell Division; D015536:Down-Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D007377:Interleukin-3; D007546:Isoquinolines; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D010566:Virulence Factors, Bordetella; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C053177:N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide; D037342:Pertussis Toxin; D011493:Protein Kinase C