Deregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor in murine macrophage cell line...

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.