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Neuropeptide-induced secretion from human skin mast cells
M K Church1, S el-Lati, J P Caulfield
1Immunopharmacology Group, Southampton General Hospital, UK.
International Archives of Allergy and Applied Immunology
|January 1, 1991
Summary
Human skin mast cells release histamine differently depending on the trigger. IgE-dependent and neuropeptide stimulation use distinct biochemical pathways but result in the same release mechanism.
Area of Science:
- Immunology
- Cell Biology
- Dermatology
Background:
- Human mast cells are found on mucosal surfaces and in the skin.
- Skin mast cells respond to various stimuli, including neuropeptides and immunological triggers.
- Histamine release is a key function of mast cells, involved in allergic and inflammatory responses.
Purpose of the Study:
- To investigate the distinct biochemical pathways of histamine release from human skin mast cells induced by IgE-dependent versus neuropeptide stimulation.
- To compare the intracellular signaling mechanisms, including calcium and cyclic AMP dynamics, following different mast cell activation methods.
- To elucidate the final common pathway of mediator secretion, specifically degranulation, in response to these diverse stimuli.
Main Methods:
- Stimulation of human skin mast cells with anti-IgE (immunological) and neuropeptides (substance P, vaso-active intestinal polypeptide, somatostatin).
- Measurement of histamine release.
- Analysis of intracellular calcium and cyclic AMP levels.
- Electron microscopy to examine degranulation morphology.
Main Results:
- Neuropeptide stimulation led to rapid histamine release with minimal eicosanoid generation, contrasting with IgE-dependent release.
- Calcium influx originated extracellularly for anti-IgE but intracellularly for neuropeptide stimulation.
- Cyclic AMP elevation patterns differed, with neuropeptide-induced increases occurring independently of extracellular calcium.
- Despite biochemical differences, both stimuli resulted in degranulation via compound exocytosis, indistinguishable ultrastructurally.
Conclusions:
- IgE-dependent and neuropeptide stimulation activate distinct intracellular signaling cascades in human skin mast cells.
- These divergent pathways converge to a common final mechanism of exocytosis for mediator release.
- Understanding these pathways is crucial for targeted therapeutic interventions in skin inflammatory conditions.