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Transforming growth factor beta 1 functions in monocytic differentiation of hematopoietic cells through autocrine and paracrine mechanisms. 1996

J M Turley, and L A Falk, and F W Ruscetti, and J J Kasper, and T Francomano, and T Fu, and O S Bang, and M C Birchenall-Roberts
Laboratory of Leukocyte Biology, National Cancer Institute, Frederick, Maryland 21702, USA.

This study examined the role of transforming growth factor beta 1 (TGF-beta 1) in monocytic differentiation of hematopoietic cells. TGF-beta 1 and retinoic acid (RA) inhibited HL-60 cell growth in a dose-dependent fashion. Treatment of HL-60 cells with a combination of TGF-beta 1 and a 50% optimal dose of RA (RA + TGF-beta 1) resulted in increased growth suppression compared to the individual treatments. Morphological studies revealed that TGF-beta 1 induced promonocytic differentiation (68%), RA induced granulocytic differentiation (98%), and RA + TGF-beta 1 induced monocytic (54%) and granulocytic (46%) differentiation of HL-60 cells. Induction of the monocyte-specific marker, nonspecific esterase, was markedly increased by TGF-beta 1 and RA + TGF-beta 1 treatment but not by RA treatment. Both TGF-beta 1 treatment and RA treatment increased TGF-beta ligand and TGF-beta receptor protein and mRNA levels. To determine whether RA mediated HL-60 cell growth inhibition and differentiation through the autocrine expression of TGF-beta 1, experiments using TGF-beta 1 antisense oligonucleotides or TGF-beta 1-neutralizing antibodies were conducted. TGF-beta 1 antisense oligonucleotides and neutralizing antibodies partially blocked RA-induced inhibition of proliferation, and TGF-beta 1 antisense oligonucleotides reversed RA-induced granulocytic maturation, demonstrating that RA signals autocrine expression of TGF-beta 1 and TGF-beta receptors. The effect of TGF-beta 1 on normal hematopoiesis was also studied using primary human fetal liver cells. TGF-beta 1 alone and in the presence of interleukin 3 promoted macrophage differentiation of primitive fetal liver cells. Cell surface expression of the monocyte/macrophage-specific marker c-fms was increased 3.1-fold following TGF-beta 1 treatment. In addition, TGF-beta 1-treated cells displayed a 51% increase in phagocytosis as compared to interleukin 3-treated control cells. These studies define a role for TGF-beta 1 in the autocrine and paracrine regulation of monocyte/macrophage differentiation.

UI MeSH Term Description Entries
D007377 Interleukin-3 A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Burst-Promoting Factor, Erythrocyte,Colony-Stimulating Factor 2 Alpha,Colony-Stimulating Factor, Mast-Cell,Colony-Stimulating Factor, Multipotential,Erythrocyte Burst-Promoting Factor,IL-3,Mast-Cell Colony-Stimulating Factor,Multipotential Colony-Stimulating Factor,P-Cell Stimulating Factor,Eosinophil-Mast Cell Growth-Factor,Hematopoietin-2,Burst Promoting Factor, Erythrocyte,Colony Stimulating Factor, Mast Cell,Colony Stimulating Factor, Multipotential,Eosinophil Mast Cell Growth Factor,Erythrocyte Burst Promoting Factor,Hematopoietin 2,Interleukin 3,Multipotential Colony Stimulating Factor,P Cell Stimulating Factor
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D010587 Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES). Phagocytoses
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004950 Esterases Any member of the class of enzymes that catalyze the cleavage of an ester bond and result in the addition of water to the resulting molecules. Esterase
D006098 Granulocytes Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS. Granulocyte
D006410 Hematopoiesis The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY). Hematopoiesis, Medullary,Haematopoiesis,Medullary Hematopoiesis

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