Macrophage inflammatory protein-1α enhances growth factor-stimulated phosphatidylcholine metabolism and increases cAMP levels in the human growth factor-dependent cell line M07e, events associated with growth suppression

C. Mantel, S. Aronica, Z. Luo, M. S. Marshall, June Kim Young June Kim, S. Cooper, N. Hague, H. E. Broxmeyer

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20 Scopus citations


The immunoregulatory C-C chemokine, macrophage inflammatory protein-1α (MIP-1α) has suppressive activity on proliferation of stem cells and early subsets of myeloid progenitor cells. A receptor for C-C chemokines that binds MIP-1α has been characterized, cloned, and shown to be related structurally to neuropeptide receptors that couple through G-proteins to phospholipase-C and adenyl cyclase. Yet, very little information on the intracellular mechanisms of action of MIP-1α is available. We show here that the human factor-dependent cell line M07e is responsive to the cell cycle-suppressive effects of MIP-1α, has specific membrane-binding sites for MIP-1α, and that treatment of these cells with this chemokine increases the phosphatidylcholine (PC) and phosphocholine turnover rates in cells that are synergistically stimulated by the combination of granulocyte-macrophage colony-stimulating factor and steel factor but not by these factors acting singly. Additionally, MIP-1α treatment induces a dose- and time-dependent increase in intracellular cAMP levels in M07e cells. Both exogenous PC and dibutyryl cAMP were found to suppress the proliferation of M07e colony-forming cells to a level similar to that of MIP-1α, further implicating cAMP and PC metabolism in MIP-1α-induced M07e suppression. RANTES, a related chemokine, with weak or incomplete binding to the cloned MIP-1α receptor, did not suppress M07e colony-forming cells, nor did it increase intracellular cAMP levels, but it did enhance growth factor-induced PC turnover, further supporting the involvement of cAMP in MIP-1α suppression while demonstrating that increased PC turnover alone is not sufficient for suppression. These findings support the idea that the human MIP-1α receptor is coupled to phospholipid and cAMP metabolism in a manner similar to other 7-transmembrane, G-protein-linked receptors and suggest that a phosphatidylcholine hydrolytic cycle and an associated increase in cAMP are part of the mechanisms of action of MIP-1α.

Original languageEnglish (US)
Pages (from-to)2342-2350
Number of pages9
JournalJournal of Immunology
Issue number5
StatePublished - Jan 1 1995


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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