Effects of prostaglandin D₂ and the DP₁ and DP₂ receptors in eosinophil recruitment into the Brown Norway rat lungs

The accumulation of eosinophils at sites of inflammation is one of the hallmarks of asthma. The aim of the present study was to investigate the involvement of PGD2 and the DP1 and DP2 receptors in eosinophil recruitment in vivo. In this project, a group of Brown Norway rats were administered intratracheally with PGD2, which activates both DP1 and DP2 receptors, as well as selective agonists of DP1 (BW245C) and DP2 (15R-methyl-PGD 2 and 13,14-dihydro-15-oxo-PGD2) receptors. In addition, we have also tested the effect of 15-deoxy-Delta12,14-PGJ 2 which known to activate PPARgamma and NF-kappaB, and DP2 receptors. Negative control animals received saline alone while positive control animals received 5-oxo-ETE. In this work, we have shown for the first time that PGD2 and selective DP2 receptor agonists induce pulmonary eosinophilia in vivo in the following order of potency; (15R-methyl-PGD 2 > PGD2 ≈ 15-deoxy-Delta12,14-PGJ 2 > dhk-PGD2). This effect was time dependent with the maximal response being observed after 24 h. Interestingly; this response was somehow diminished when higher dose was tested (10mug). This effect is most likely to be mediated solely through the DP2 receptor since this effect was not shared by the DP1 specific agonist BW245C. These results are consistent with an important role for PGD2 and the DP 2 receptor/CRTH2 in allergic diseases such as asthma and suggest that this receptor may be an important therapeutic target for these conditions