Deregulation of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor in murine macrophage cell line J774A.1

✍ Scribed by Kai Fan; Nelleke Barendsen; Lyle Sensenbrenner; Ben D. M. Chen

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 781 KB
• Volume: 154
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041540312

✦ Synopsis

j774A. 1 immortalized macrophage tumor cells display several phenotypes and functional capacities similar to that of murinc 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 l774A.1 cells can be further enhanced in the presence of exogenous rMuGM-CSF, rHuM-CSF, and rMulL-3. Treatment with either rMulL-3 (20 ng/ml) and rHuTGF-Pl (1.0 ng/ml) for 24 hr at 37"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 (20-1 00 ngiml) or H-8 (50 p,M) for 24 hr led to an enhanced expression of GM-CSF receptors on 1774A.1 cells in a timeand 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 cclls, such regulatory interaction may not exist.