Human mast cells release the migraine-inducing factor pituitary adenylate cyclase-activating polypeptide (PACAP)
| Autor: | David C. DeRosa, Angela J. Okragly, Kirk W. Johnson, Michael P. Johnson, Andrea P. Martin, Robert J. Benschop, S Michelle Morin |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Allergy Migraine Disorders Adenylate kinase Neuropeptide 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Human Umbilical Vein Endothelial Cells Humans Mast Cells Receptor Cells Cultured Dose-Response Relationship Drug business.industry Degranulation Biological activity General Medicine medicine.disease Cell biology 030104 developmental biology Endocrinology Cell culture Immunohistochemistry Pituitary Adenylate Cyclase-Activating Polypeptide Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | Cephalalgia : an international journal of headache. 38(9) |
| ISSN: | 1468-2982 |
| Popis: | Background Many patients with migraines suffer from allergies and vice versa, suggesting a relationship between biological mechanisms of allergy and migraine. It was proposed many years ago that mast cells may be involved in the pathophysiology of migraines. We set out to investigate the relationship between mast cell activation and known neurogenic peptides related to migraine. Methods Cultured human mast cells were assayed for the presence of neuropeptides and their receptors at the RNA and protein level. Immunohistochemistry analyses were performed on tissue resident and cultured mast cells. Mast cell degranulation assays were performed and pituitary adenylate cyclase-activating polypeptide (PACAP) activity was measured with a bioassay. Results We found that cultured and tissue resident human mast cells contain PACAP in cytoplasmic granules. No other neurogenic peptide known to be involved in migraine was detected, nor did mast cells express the receptors for PACAP or other neurogenic peptides. Furthermore, mast cell degranulation through classic IgE-mediated allergic mechanisms led to the release of PACAP. The PACAP released from mast cells was biologically active, as demonstrated using PACAP receptor reporter cell lines. We confirmed existing literature that mast cell degranulation can also be induced by several neurogenic peptides, which also resulted in PACAP release. Conclusion Our data provides a potential biological explanation for the association between allergy and migraine by demonstrating the release of biologically active PACAP from mast cells. |
| Databáze: | OpenAIRE |
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