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Analyzing the Functions of Mast Cells In Vivo Using 'Mast Cell Knock-in' Mice
Published on: May 27, 2015
Effect of the c-kit Ligand on Mediator Release by Human Lung Mast Cells
Insights
The c-kit ligand (KL) triggers human mast cells (MC) after culture, enhancing IgE-dependent responses. This cytokine may regulate mast cell-associated diseases like asthma.
Area of Science:
- Immunology
- Cell Biology
Background:
- Cytokine modulation of human lung mast cells (MC) is not well understood.
- The c-kit ligand (KL) was previously shown to modulate IgE-dependent mediator release in freshly isolated human lung MC.
Purpose of the Study:
- To investigate the effect of KL on cultured human lung MC.
- To compare the functional responsiveness of human and rodent MC to cytokines.
Main Methods:
- Human lung MC were cultured for several days.
- The effect of KL on mediator release (histamine, leukotrienes) from cultured MC was assessed.
- IgE-dependent responses in cultured MC were evaluated.
Main Results:
- KL induced significant mediator release from cultured MC without additional stimuli.
- Cultured MC exhibited a strongly enhanced IgE-dependent response compared to freshly isolated cells.
- Human and rodent MC showed distinct functional responses to cytokines.
Conclusions:
- KL acts as a potent trigger for cultured human lung MC.
- Cytokine responsiveness differs significantly between human and rodent MC.
- KL may play a crucial role in mast cell-associated diseases, including asthma.
Abstract:
IgE-independent mediator release or modulation of mediator release by cytokines has not been described for human lung mast cells (MC) so far. We recently showed that among a large number of cytokines examined the c-kit ligand (KL) is a unique cytokine capable of modulating histamine and leukotriene release in human lung mast cells. KL increases the IgE-dependent mediator release 2- to 3-fold without inducing substantial mediator release over the control by itself in freshly isolated cells. By contrast, this study shows that KL becomes a potent triggering agent per se in MC cultured for a few days without addition of KL or feeder cells. Furthermore, the IgE-dependent response is strongly enhanced after culture. The present study indicates that human and rodent MC differ strongly in their functional repsonsiveness towards cytokines, and that KL may be an important regulator of mast cell-associated disease, such as asthma.
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