Prostaglandin D2 reinforces Th2 type inflammatory responses of airways to low-dose antigen through bronchial expression of macrophage-derived chemokine

PGD(2) a lipid mediator released from mast cells, is known to participate in allergic reactions. However, the mechanism by which PGD(2) contributes to such reactions remains unclear. We established a novel experimental model of asthma that permitted direct assessment of the role of PGD(2) in airway inflammation. Antigen-sensitized mice were exposed to aerosolized prostaglandin D-2 (PGD(2)) 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 PGD(2)-pretreated mice than in control mice. The expression of macrophage-derived chemokine (MDC), a chemoattractant for Th2 cells, was greater in PGD(2)-pretreated mice than in control. Injection of anti-MDC antibody into PGD(2)-pretreated mice markedly inhibited inflammatory cell infiltration as well as Th2 cytokine production after antigen challenge. These results indicate that PGD(2) 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.