Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice.
PGD(2) 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 PGD(2) 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, PGD(2), but not PGE(2), substantially increased in the lungs of WT and TG mice with greater PGD(2) 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-gamma 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-gamma than those from WT mice, whereas IL-4 production was unchanged between WT and TG mice. Thus, overproduction of PGD(2) 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 PGD(2) plays an important role in late phase allergic reactions in the pathophysiology of bronchial asthma.
Fujitani
Yasushi
Y
Core Research for Evolutional Science and Technology, Japan Science and Technology Corp., Suita, Osaka, Japan. Fujitani_Yasushi@takeda.co.jp
Kanaoka
Yoshihide
Y
Aritake
Kosuke
K
Uodome
Nobuko
N
Okazaki-Hatake
Kazue
K
Urade
Yoshihiro
Y
D000818:Animals; D001249:Asthma / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007124:Immunoenzyme Techniques; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D007958:Leukocyte Count; D054834:Lipocalins; D008168:Lung / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D015230:Prostaglandin D2 / Q000096:biosynthesis; D011657:Pulmonary Eosinophilia / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000096:biosynthesis / Q000235:genetics; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology*; D015854:Up-Regulation
D018925:Chemokines; D016207:Cytokines; D054834:Lipocalins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D010047:Ovalbumin; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor