Modulation by tumor necrosis factor-α of human astroglial cell production of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF)

Monocyte expression and secretion of tumor necrosis factor (TNF) and TNF receptors (TNF-R) p55 and p75 was studied in patients receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) after intensive chemotherapy. TNF expression and secretion of biologically active TNF was increased at regeneration compared with that of patients who had received chemotherapy alone. This effect persisted for several weeks after cessation of growth factor therapy. GM-CSF restored the responsiveness of monocytes to bacterial lipopolysaccharide (LPS), which appeared to be diminished after chemotherapy alone. Expression and secretion of TNF-R p55 and p75 by monocytes was augmented by GM-CSF therapy in association with the increase in TNF protein. We propose that GM-CSF administration after chemotherapy restores the normal responsiveness of monocytes to a secondary stimulus such as LPS and primes monocytes to respond to LPS with increased expression and secretion of TNF and TNF-R.

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Tyrosine phosphorylation and intracellular alkalinization are early events in human neutrophils stimulated by tumor necrosis factor, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor

Biochimica et Biophysica Acta (BBA) - General Subjects ◽

10.1016/0304-4165(93)90136-v ◽

1993 ◽

Vol 1156 (2) ◽

pp. 197-203 ◽

Cited By ~ 29

Author(s):

Akira Yuo ◽

Seiichi Kitagawa ◽

Eriko Azuma ◽

Yasuhiro Natori ◽

Atsushi Togawa ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Human Neutrophils ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor ◽

Intracellular Alkalinization ◽

Necrosis Factor

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Mechanisms of tumor necrosis factor-granulocyte-macrophage colony- stimulating factor-induced dendritic cell development

Blood ◽

10.1182/blood.v82.10.3019.3019 ◽

1993 ◽

Vol 82 (10) ◽

pp. 3019-3028 ◽

Cited By ~ 65

Author(s):

F Santiago-Schwarz ◽

N Divaris ◽

C Kay ◽

SE Carsons

Keyword(s):

Dendritic Cell ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Cell Development ◽

Colony Stimulating Factor ◽

Gm Csf ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor ◽

Necrosis Factor

Abstract In a previous report, we described that tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) synergistically enhanced the development of dendritic cell (DC) progeny from early stem cells and that there is a common monocyte-DC progenitor cell. Low levels of DC were obtained with GM-CSF alone, and TNF by itself failed to induce stem cell development. Here, we investigate mechanisms by which TNF and GM-CSF institute increases in DC, and how these same molecules support later stages of DC differentiation. We show that TNF is required as the first signal, that there is upregulation of GM-CSF receptors (GM-CSFRs), and that TNF inhibits the differentiation of colony-forming units-granulocyte. High levels of GM- CSFR were always associated with conditions yielding a large number of DC, and a kinetic analysis showed a close ontogenic relationship between DC and GM-CSFR levels. The addition of anti-GM-CSF or anti-TNF antibodies blocked synergistic responses related to DC development, including high levels of GM-CSFRs. Anti-GM-CSF was the most potent inhibitor of proliferation (80%) and macrophage, DC, and polymorphonuclear (PMN) cell development. With polyclonal anti-TNF, inhibition was less (35%), and there was a shift from myelomonocytic and DC to PMN progeny. Our results support the concept that receptor upregulation is an important mechanism for growth factor synergy. Our data also indicate that the opposing effects of TNF on hematopoiesis contribute to the selection of the DC pathway and emphasize the importance of GM-CSFRs not only in initiated DC development, but also in controlling DC viability and function.

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