Platelet-Activating Factor–Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2–Dependent Mechanisms
| Autor: | Eric J. Romer, Garret A. FitzGerald, Jesus A. Ocana, Sven-Christian Pawelzik, Ravi P. Sahu, Jeffrey B. Travers, Mark H. Kaplan |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Cell type Carboxy-Lyases Immunology Dermatitis Contact Dinoprostone Article Receptors G-Protein-Coupled Proinflammatory cytokine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement medicine Animals Immunology and Allergy Mast Cells Platelet Activating Factor Receptor Immunosuppression Therapy Platelet-activating factor biology Mast cell Histidine decarboxylase Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure chemistry Cyclooxygenase 2 Cancer research biology.protein Female lipids (amino acids peptides and proteins) Lymph Nodes Cyclooxygenase Histamine 030215 immunology |
| Zdroj: | The Journal of Immunology. 200:4004-4011 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1701145 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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