Prostaglandin D_2 (PGD_2), a mast cell-derived lipid mediator is detected in lage amounts in airways of asthmatics, but its role of largely unkown. To clarify the role of PGD_2 in Th2-type airway inflammation which characterizes asthma, we studied the effects of aerosolized PGD_2 on the inflammatory response to a low-dose antien challenge in airways of mice. Mice sensitized with ovalbumin (OVA) were challenged with a conventional-dose (1%) or a low dose (0.1%) aerosolized OVA. Mice received low - dose OVA challenge were pretreated with aerosolized PGD_2 (10^M) (PGD_2 plus low-dose OVA mice) or saline (low-dose OVA alone mice) 24 hrs before the OVA challenge. Some mice were pretreated with PGD_2 but challenged with saline (PGD_2 alone mice). Airway inflammation was evaluated by the numbers of eosinophils, lymphocytes and macrophages in bronchoalveolar lavage fluid. The degree of airway inflammation in the PGD_2 alone mice and the low-dose OVA alone mice were only marginal. However, the PGD_2 plus low-dose OVA mice displayed a similar degree of airway inflammation with mice received conventional-dose OVA challenge. Levels of interleukin (IL)-4 and IL-5 were significantly increased in the PGD_2 plus low-dose OVA mice than the low-dose OVA alone mice. PGD_2 (10^-10^ M) did not affect the Th2-type cytokine production by OVA specific T cells in response to OVA stimulation in vitro. Immunohistochemical analysis of lung tissue revealed that airway epithelium of the PGD_2 plus low-dose OVA alone mice were strongly stained with monoclonal antibody against macrophage-derived chemokine (MDC), a Th2 cell-specific chemokine. These results suggest that PGD_2 augments Th2 cell -type airway inflammation via epithelial experssion of MDC
