Journal article
Enhancement of Mast Cell Degranulation Mediated by Purinergic Receptors' Activation and PI3K Type delta
The Journal of immunology (1950), v 207(4), pp 1001-1008
15 Aug 2021
PMID: 34330752
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Mast cells express multiple metabotropic purinergic P2Y receptor (P2YR) subtypes. Few studies have evaluated their role in human mast cell (HMC) allergic response as quantified by degranulation induced by cross-linking the high-affinity IgE receptor (Fc epsilon RI). We have previously shown that extracellular nucleotides modify the Fc epsilon RI activation-dependent degranulation in HMCs derived from human lungs, but the mechanism of this action has not been fully delineated. This study was undertaken to determine the mechanism of activation of P2YRs on the degranulation of HMCs and elucidate the specific postreceptor pathways involved. Sensitized LAD2 cells, a human-derived mast cell line, were subjected to a weak allergic stimulation (WAS) using a low concentration of Ag in the absence and presence of P2YR agonists. Only the metabotropic purinergic P2Y11 receptor (P2Y11R) agonist, adenosine 5'-(3-thio)triphosphate (ATP gamma S), enhanced WAS-induced degranulation resulting in a net 7-fold increase in release (n = 4; p < 0.01). None of the P2YR agonists tested, including high concentrations of ATP gamma S (1000 mu M), enhanced WAS-induced intracellular Ca2+ mobilization, an essential component of activated Fc epsilon RI-induced degranulation. Both a PI3K inhibitor and the relevant gene knockout decreased the ATP gamma S-induced enhancement. The effect of ATP gamma S was associated with enhanced phosphorylation of PI3K type delta and protein kinase B, but not the phosphoinositide-dependent kinase-1. The effects of ATP gamma S were dose dependently inhibited by NF157, a P2Y11R antagonist. To our knowledge, these data indicate for the first time that P2YR is linked to enhancement of allergic degranulation in HMC via the PI3K/protein kinase B pathway.
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Details
- Title
- Enhancement of Mast Cell Degranulation Mediated by Purinergic Receptors' Activation and PI3K Type delta
- Creators
- Haruhisa Nishi - Jikei University School of MedicineFrancois Niyonsaba - Juntendo UniversityAmir Pelleg - Danmir Therapeutics, LLC, Haverford, PA; and.Edward S. Schulman - Drexel University
- Publication Details
- The Journal of immunology (1950), v 207(4), pp 1001-1008
- Publisher
- American Association of Immunologists
- Number of pages
- 9
- Grant note
- LIXIL Jyukankyo Foundation Margaret Wolf Research Endowment Jikei University Research Fund; Jikei University
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pulmonary, Critical Care, and Sleep (Medicine)
- Web of Science ID
- WOS:000731567400002
- Scopus ID
- 2-s2.0-85112259844
- Other Identifier
- 991019168477204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology