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Granulocyte-macrophage colony-stimulating factor plays a role in the functional activity of mast cells
R Meade1, K M Neddermann, R S Greenfield
1Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660.
Abstract:
A peptide homologous to a region of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF), P27-38, which was shown to be a GM-CSF antagonist, inhibited the function of serotonin release from murine mast cells. Peptide P27-38 inhibited immunoglobulin E (IgE)-mediated serotonin release in a dose-dependent manner when induced by either specific antigen or anti-IgE antibody. In contrast, non-receptor-mediated release of serotonin by agents such as compound 48/80 or the calcium ionophore A23187 were not affected by the GM-CSF antagonist. Similar effects were observed with GM-CSF-neutralizing antibodies. The inhibitory effect of P27-38 and the neutralizing antibodies on serotonin release could be reversed by the addition of exogenous GM-CSF to the stimulated mast cells, indicating that the inhibitory activity was probably due to an effect on endogenously produced GM-CSF. These findings suggest that GM-CSF produced by stimulated mast cells is involved in the regulation of their activity in an autocrine manner.
Insights
A peptide antagonist of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) inhibited IgE-mediated serotonin release from mast cells. This suggests endogenous mGM-CSF regulates mast cell activity in an autocrine manner.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Mast cells play a crucial role in allergic responses.
- Granulocyte-macrophage colony-stimulating factor (GM-CSF) is implicated in mast cell function.
- The role of endogenously produced GM-CSF in mast cell activity requires further elucidation.
Purpose of the Study:
- To investigate the role of murine granulocyte-macrophage colony-stimulating factor (mGM-CSF) in regulating serotonin release from murine mast cells.
- To determine if mGM-CSF produced by mast cells acts in an autocrine fashion.
Main Methods:
- Utilized a peptide antagonist (P27-38) homologous to mGM-CSF to inhibit its function.
- Stimulated mast cells with specific antigen, anti-IgE antibody, compound 48/80, or calcium ionophore A23187.
- Assessed serotonin release in response to these stimuli and the presence of P27-38 or mGM-CSF neutralizing antibodies.
- Investigated the effect of exogenous mGM-CSF on reversing the inhibitory activity.
Main Results:
- Peptide P27-38 dose-dependently inhibited immunoglobulin E (IgE)-mediated serotonin release induced by antigen or anti-IgE.
- Non-receptor-mediated serotonin release (compound 48/80, A23187) was unaffected by P27-38.
- GM-CSF-neutralizing antibodies showed similar inhibitory effects on IgE-mediated serotonin release.
- The inhibitory effects of P27-38 and neutralizing antibodies were reversible by adding exogenous mGM-CSF.
Conclusions:
- Endogenously produced mGM-CSF by stimulated mast cells plays a significant role in regulating their activity.
- Mast cell function, specifically IgE-mediated serotonin release, is regulated in an autocrine manner by mGM-CSF.
- These findings highlight a novel autocrine feedback loop involving mGM-CSF in mast cell biology.