Platelet-activating factor-induced reduction in contact hypersensitivity responses is mediated by mast cells via cyclooxygenase-2-dependent mechanisms

Jesus A. Ocana, Eric Romer, Ravi Sahu, Sven Christian Pawelzik, Garret A. FitzGerald, Mark H. Kaplan, Jeffrey B. Travers

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Platelet-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 PGE 2 release. Importantly, PAFR-mediated systemic immunosuppression was defective in mice that lackedMCs, 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 PGE 2 -dependent mechanisms.

Original languageEnglish (US)
Pages (from-to)4004-4011
Number of pages8
JournalJournal of Immunology
Volume200
Issue number12
DOIs
StatePublished - Jun 15 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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