Prostaglandin D₂ Reinforces Th2 Type Inflammatory Responses of Airways to Low-dose Antigen through Bronchial Expression of Macrophage-derived Chemokine

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.