Human mast cells release the migraine-inducing factor pituitary adenylate cyclase-activating polypeptide (PACAP)

Cephalalgia : an International Journal of Headache
Angela J OkraglyRobert J Benschop

Abstract

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. W...Continue Reading

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Citations

Jul 14, 2019·Cephalalgia : an International Journal of Headache·Hashmat GhanizadaMessoud Ashina
Jan 16, 2019·The Journal of Pharmacology and Experimental Therapeutics·Cristina Moldovan LoomisLeon F Garcia-Martinez
Mar 1, 2018·Frontiers in Cellular Neuroscience·Olivia C Eller-SmithJulie A Christianson
Jan 25, 2020·Cephalalgia : an International Journal of Headache·Claire HuangShuu-Jiun Wang
Jun 4, 2020·Cephalalgia : an International Journal of Headache·Jacob Carl Alexander EdvinssonKristian Agmund Haanes
Apr 27, 2019·Frontiers in Cellular Neuroscience·Duygu Koyuncu IrmakFatma Tore
Feb 16, 2019·The Journal of Headache and Pain·Francesco De LoguRomina Nassini
Feb 12, 2021·Cephalalgia : an International Journal of Headache·Nita Katarina Frifelt WienholtzMessoud Ashina
Aug 20, 2021·Journal of Inflammation Research·Angela J OkraglyRobert J Benschop

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Methods Mentioned

BETA
FACS
flow cytometry
biopsies
ELISA

Software Mentioned

FlowJo
GraphPad Prism

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