Pronounced Eosinophilic Lung Inflammation and Th2 Cytokine Release in Human Lipocalin-Type Prostaglandin D Synthase Transgenic Mice
| Autor: | Kazue Okazaki-Hatake, Yoshihiro Urade, Nobuko Uodome, Yasushi Fujitani, Yoshihide Kanaoka, Kosuke Aritake |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Eotaxin
Genetically modified mouse medicine.medical_specialty Chemokine Ovalbumin Transgene Receptors Prostaglandin Immunology Mice Transgenic Inflammation Immunoglobulin E Immunoenzyme Techniques Leukocyte Count Mice Th2 Cells Internal medicine medicine Animals Humans Immunology and Allergy RNA Messenger Pulmonary Eosinophilia Receptors Immunologic Lung Sensitization biology medicine.diagnostic_test Prostaglandin D2 Chemistry respiratory system Asthma Lipocalins Up-Regulation respiratory tract diseases Intramolecular Oxidoreductases Endocrinology Bronchoalveolar lavage medicine.anatomical_structure biology.protein Cytokines lipids (amino acids peptides and proteins) Chemokines medicine.symptom Bronchoalveolar Lavage Fluid |
| Zdroj: | The Journal of Immunology. 168:443-449 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.168.1.443 |
| Popis: | PGD2 is a major lipid mediator released from mast cells, but little is known about its role in the development of allergic reactions. We used transgenic (TG) mice overexpressing human lipocalin-type PGD synthase to examine the effect of overproduction of PGD2 in an OVA-induced murine asthma model. The sensitization of wild-type (WT) and TG mice was similar as judged by the content of OVA-specific IgE. After OVA challenge, PGD2, but not PGE2, substantially increased in the lungs of WT and TG mice with greater PGD2 increment in TG mice compared with WT mice. The numbers of eosinophils and lymphocytes in the bronchoalveolar lavage (BAL) fluid were significantly greater in TG mice than in WT mice on days 1 and 3 post-OVA challenge, whereas the numbers of macrophages and neutrophils were the same in both WT and TG mice. The levels of IL-4, IL-5, and eotaxin in BAL fluid were also significantly higher in TG mice than in WT mice, although the level of IFN-γ in the BAL fluid of TG mice was decreased compared with that in WT mice. Furthermore, lymphocytes isolated from the lungs of TG mice secreted less IFN-γ than those from WT mice, whereas IL-4 production was unchanged between WT and TG mice. Thus, overproduction of PGD2 caused an increase in the levels of Th2 cytokines and a chemokine, accompanied by the enhanced accumulation of eosinophils and lymphocytes in the lung. These results indicate that PGD2 plays an important role in late phase allergic reactions in the pathophysiology of bronchial asthma. |
| Databáze: | OpenAIRE |
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