Platelet-Activating Factor-Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2-Dependent Mechanisms

dc.contributor.authorOcana, Jesus A.
dc.contributor.authorRomer, Eric
dc.contributor.authorSahu, Ravi
dc.contributor.authorPawelzik, Sven-Christian
dc.contributor.authorFitzGerald, Garret A.
dc.contributor.authorKaplan, Mark H.
dc.contributor.authorTravers, Jeffrey B.
dc.contributor.departmentPharmacology and Toxicology, School of Medicineen_US
dc.date.accessioned2019-08-28T18:46:07Z
dc.date.available2019-08-28T18:46:07Z
dc.date.issued2018-06-15
dc.description.abstractPlatelet-activating factor (PAF) stimulates numerous cell types via activation of the G protein-coupled PAF receptor (PAFR). PAFR activation not only induces acute proinflammatory responses, but it also induces delayed systemic immunosuppressive effects by modulating host immunity. Although enzymatic synthesis and degradation of PAF are tightly regulated, oxidative stressors, such as UVB, chemotherapy, and cigarette smoke, can generate PAF and PAF-like molecules in an unregulated fashion via the oxidation of membrane phospholipids. Recent studies have demonstrated the relevance of the mast cell (MC) PAFR in PAFR-induced systemic immunosuppression. The current study was designed to determine the exact mechanisms and mediators involved in MC PAFR-mediated systemic immunosuppression. By using a contact hypersensitivity model, the MC PAFR was not only found to be necessary, but also sufficient to mediate the immunosuppressive effects of systemic PAF. Furthermore, activation of the MC PAFR induces MC-derived histamine and PGE2 release. Importantly, PAFR-mediated systemic immunosuppression was defective in mice that lacked MCs, or in MC-deficient mice transplanted with histidine decarboxylase- or cyclooxygenase-2-deficient MCs. Lastly, it was found that PGs could modulate MC migration to draining lymph nodes. These results support the hypothesis that MC PAFR activation promotes the immunosuppressive effects of PAF in part through histamine- and PGE2-dependent mechanisms.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationOcana, J. A., Romer, E., Sahu, R., Pawelzik, S. C., FitzGerald, G. A., Kaplan, M. H., & Travers, J. B. (2018). Platelet-Activating Factor-Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2-Dependent Mechanisms. Journal of immunology (Baltimore, Md. : 1950), 200(12), 4004–4011. doi:10.4049/jimmunol.1701145en_US
dc.identifier.urihttps://hdl.handle.net/1805/20679
dc.language.isoen_USen_US
dc.publisherAmerican Association of Immunologistsen_US
dc.relation.isversionof10.4049/jimmunol.1701145en_US
dc.relation.journalJournal of Immunologyen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectMast cellsen_US
dc.subjectCyclooxygeneaseen_US
dc.subjectPlatelet-activating factoren_US
dc.subjectHistamineen_US
dc.subjectHistidine decarboxylaseen_US
dc.titlePlatelet-Activating Factor-Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2-Dependent Mechanismsen_US
dc.typeArticleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
nihms958249.pdf
Size:
1.92 MB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.99 KB
Format:
Item-specific license agreed upon to submission
Description: