Cell-cell interactions modulate the responsiveness of PC12 cells to nerve growth factor

The growth of PC12 cells on a collagen substratum or on monolayers of several non-neuronal cell types was studied by measuring nerve growth factor (NGF)-dependent increases in the expression of a 150 X 10(3) (Mr) neurofilament protein subunit and the membrane glycoprotein Thy-1. Both responses were found to be greatly suppressed in cultures of fibroblasts as compared to the C2 and G8-1 muscle cell lines and the C6 glioma cell line. This suppression was associated with an inhibition of NGF-dependent neuritic outgrowth from PC12 cells grown on fibroblast monolayers. There was no evidence that fibroblasts secrete soluble molecules that directly inhibit these responses or neutralize NGF. In addition, there was no difference in the neurofilament protein response from PC12 cells that had been treated with NGF prior to coculture, and the now primed PC12 cells readily extended axons over fibroblast monolayers. These data demonstrate that cell-cell and/or cell-matrix interactions can modulate biochemical responses to NGF and suggest that responsiveness of neuronal cells to environmental cues is not immutable. Control of the latter may be at the level of expression of receptor molecules for cell-surface- or matrix-associated macromolecules and a similar mechanism operating during development could play a role in growth cone guidance.

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Effect of nerve growth factor on the release of inflammatory mediators by mature human basophils

Blood ◽

10.1182/blood.v79.10.2662.2662 ◽

1992 ◽

Vol 79 (10) ◽

pp. 2662-2669 ◽

Cited By ~ 4

Author(s):

SC Bischoff ◽

CA Dahinden

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Inflammatory Mediators ◽

Ganglion Cells ◽

Neuronal Cell ◽

Cell Types ◽

Cell Fractionation ◽

Hematopoietic Growth Factors ◽

Nerve Growth ◽

Human Basophils

Abstract Nerve growth factor (NGF) is a neurotrophic cytokine known to regulate the survival and function of peripheral and central neuronal cells. Recently, the spectrum of action could be extended to non-neuronal cell types such as rat mast cells and human B lymphocytes. The present study shows that NGF affects the function of mature human basophils isolated from the peripheral blood of healthy donors. Both murine NGF 7S and recombinant human NGF beta enhance histamine release and strongly modulate the formation of lipid mediators by basophils in response to various stimuli. This priming effect of NGF on basophils occurs rapidly within 10 to 15 minutes of preincubation, is dose-dependent, and requires similarly low concentrations (1 to 40 pmol/L) of human NGF beta as the induction of neurite outgrowth in ganglion cells. Cell fractionation studies indicate that NGF acts directly on human basophils without an involvement of other cell types, suggesting the presence of high-affinity NGF receptors on basophils. NGF by itself (up to 4 nmol/L of human NGF beta) does not induce the release of inflammatory mediators directly. The effect of human NGF on basophil mediator release is similar to that of the hematopoietic growth factors interleukin-3, interleukin-5, and granulocyte-macrophage colony- stimulating factor. The present study further demonstrates that NGF acts as a pleiotropic cytokine at the interface between the nervous and the immune system, and that NGF may be involved in inflammatory processes and hypersensitivity reactions.

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The effect of nerve growth factor on the development of sodium channels in PC12 cells

Biochemistry and Cell Biology ◽

10.1139/o86-152 ◽

1986 ◽

Vol 64 (11) ◽

pp. 1153-1159 ◽

Cited By ~ 12

Author(s):

Juta K. Reed ◽

Diane England

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Pc12 Cells ◽

Specific Binding ◽

Neuronal Cell ◽

Scorpion Toxin ◽

Excitable Cells ◽

Response Curves ◽

Nerve Growth ◽

Differentiated Cells

We have studied the development of the action potential Na+ channels in PC12 cells, an established line that has been useful as a model for neuronal differentiation. In continuous culture PC12 cells, although electrically inexcitable, nevertheless have a low level of Na+ channels as judged by the increase in 22Na+ uptake in the presence of veratridine and scorpion toxin. These two neurotoxins have been shown to promote activation of Na+ channels in a variety of electrically excitable cells. Following treatment with nerve growth factor (NGF), conditions which induce differentiation to an electrically excitably neuronal-cell type, the neurotoxin-activated 22Na+ uptake increases approximately 12-fold, on a per cell basis, reaching a maximum in 12–16 days. The dose–response curves for veratridine and scorpion toxin are unchanged by NGF treatment (K0.5 for veratridine, 18–14 μM; K0.5 for scorpion toxin, 120–96 nM). Na+ channels in both undifferentiated and differentiated cells are tetrodotoxin sensitive and NGF treatment has no effect on the inhibition constant (Ki, 10–12 nM). Na+ channel sites were measured directly by the specific binding of [3H]saxitoxin. In NGF-treated cells, the saxitoxin receptor density reaches 154 fmol/mg protein (Kd, 1.3 nM), a level comparable to other excitable cells. Levels in control cells were too low to measure accurately. These findings show that NGF treatment of PC12 cells leads to a substantial increase in the expression of neurotoxin-sensitive Na+ channels. Furthermore, these channels are pharmacologically similar, if not identical, to those which exist in undifferentiated cells and therefore do not appear to result from the conversion of preexisting channels.

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Cholera Toxin and Dibutyryl Cyclic AMP Inhibit the Expression of Neurofilament Protein Induced by Nerve Growth Factor in Cultures of Naive and Primed PC12 Cells

Journal of Neurochemistry ◽

10.1111/j.1471-4159.1987.tb02425.x ◽

1987 ◽

Vol 49 (6) ◽

pp. 1676-1687 ◽

Cited By ~ 25

Author(s):

Patrick Doherty ◽

Derek A. Mann ◽

Frank S Walsh

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Cyclic Amp ◽

Cholera Toxin ◽

Pc12 Cells ◽

Dibutyryl Cyclic Amp ◽

Neurofilament Protein ◽

Nerve Growth

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Effect of nerve growth factor on the release of inflammatory mediators by mature human basophils

Blood ◽

10.1182/blood.v79.10.2662.bloodjournal79102662 ◽

1992 ◽

Vol 79 (10) ◽

pp. 2662-2669 ◽

Cited By ~ 160

Author(s):

SC Bischoff ◽

CA Dahinden

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Inflammatory Mediators ◽

Ganglion Cells ◽

Neuronal Cell ◽

Cell Types ◽

Cell Fractionation ◽

Hematopoietic Growth Factors ◽

Nerve Growth ◽

Human Basophils

Nerve growth factor (NGF) is a neurotrophic cytokine known to regulate the survival and function of peripheral and central neuronal cells. Recently, the spectrum of action could be extended to non-neuronal cell types such as rat mast cells and human B lymphocytes. The present study shows that NGF affects the function of mature human basophils isolated from the peripheral blood of healthy donors. Both murine NGF 7S and recombinant human NGF beta enhance histamine release and strongly modulate the formation of lipid mediators by basophils in response to various stimuli. This priming effect of NGF on basophils occurs rapidly within 10 to 15 minutes of preincubation, is dose-dependent, and requires similarly low concentrations (1 to 40 pmol/L) of human NGF beta as the induction of neurite outgrowth in ganglion cells. Cell fractionation studies indicate that NGF acts directly on human basophils without an involvement of other cell types, suggesting the presence of high-affinity NGF receptors on basophils. NGF by itself (up to 4 nmol/L of human NGF beta) does not induce the release of inflammatory mediators directly. The effect of human NGF on basophil mediator release is similar to that of the hematopoietic growth factors interleukin-3, interleukin-5, and granulocyte-macrophage colony- stimulating factor. The present study further demonstrates that NGF acts as a pleiotropic cytokine at the interface between the nervous and the immune system, and that NGF may be involved in inflammatory processes and hypersensitivity reactions.

Download Full-text