1. Prostaglandin D2 Reinforces Th2 Type Inflammatory Responses of Airways to Low-dose Antigen through Bronchial Expression of Macrophage-derived Chemokine
- Author
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Bunpei Yamaguchi, Hirokuni Hirata, Takeshi Tokuhisa, Shinsuke Taki, Gang Cheng, Fukiko Eda, Takeshi Fukuda, Kyoko Honda, Fumiya Fukushima, Masafumi Arima, and Masahiko Hatano
- Subjects
Male ,Chemokine ,Immunology ,chemokines ,Inflammation ,Article ,Bronchial Provocation Tests ,Cell Line ,Mice ,chemistry.chemical_compound ,Th2 Cells ,Antigen ,Animals ,Humans ,Immunology and Allergy ,Medicine ,Antigens ,prostanoids ,Lung ,Chemokine CCL22 ,Mice, Inbred BALB C ,integumentary system ,biology ,medicine.diagnostic_test ,Prostaglandin D2 ,business.industry ,Chemotaxis ,Lipid signaling ,epithelial cells ,Asthma ,Disease Models, Animal ,Bronchoalveolar lavage ,chemistry ,Chemokines, CC ,biology.protein ,Cytokines ,lipids (amino acids, peptides, and proteins) ,bronchial asthma ,Bronchial Hyperreactivity ,Antibody ,medicine.symptom ,business ,Bronchoalveolar Lavage Fluid ,Spleen - Abstract
PGD2, a lipid mediator released from mast cells, is known to participate in allergic reactions. However, the mechanism by which PGD2 contributes to such reactions remains unclear. We established a novel experimental model of asthma that permitted direct assessment of the role of PGD2 in airway inflammation. Antigen-sensitized mice were exposed to aerosolized prostaglandin D2 (PGD2) 1 d before challenge with low-dose aerosolized antigen. Not only the numbers of eosinophils, lymphocytes, and macrophages but also the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid were higher in PGD2-pretreated mice than in control mice. The expression of macrophage-derived chemokine (MDC), a chemoattractant for Th2 cells, was greater in PGD2-pretreated mice than in control. Injection of anti-MDC antibody into PGD2-pretreated mice markedly inhibited inflammatory cell infiltration as well as Th2 cyto-kine production after antigen challenge. These results indicate that PGD2 accelerates Th2 type inflammation by induction of MDC. Our results suggest that this mechanism may play a key role in the development of human asthma and that MDC might be a target molecule for therapeutic intervention.
- Published
- 2003
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