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Received for publication October 15, 2004.
Revised December 1, 2004.
Accepted for publication December 6, 2004.
12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats
Prostaglandin (PG) D2 is an arachidonic acid metabolite that is released by allergen-stimulated mast cells. It is a potent in vitro chemoattractant for human eosinophils, acting through the DP2 receptor/CRTH2. Furthermore, there is in vivo evidence that PGD2 contributes to allergen-induced pulmonary eosinophilia via its classic DP1 receptor. The PGD2-derived product 15-deoxy-
12,14-PGJ2 is widely used as a PPAR
agonist and has been shown to have anti-inflammatory properties. However, this substance can also activate eosinophils in vitro through the DP2 receptor. The objectives of the present study were to determine whether PGD2 and 15-deoxy-12,14-PGJ2 can induce pulmonary eosinophilia and, if so, to examine the relative effects of selective DP1 and DP2 receptor agonists on this response. Brown Norway rats were treated by intratracheal instillation of PGs. Vehicle and 5-oxo-ETE were used as negative and positive controls, respectively. Lung eosinophils were identified by immunostaining of lung sections with an antibody to major basic protein. Both PGD2 and 15-deoxy-12,14-PGJ2 induced robust eosinophilic responses that were apparent by 12 h and persisted for at least 48 h. Two selective DP2 receptor agonists, 15R-methyl-PGD2 and 13-14-dihydro-15-keto-PGD2, induced similar responses, the former being more potent than PGD2, whereas the latter was less potent. The selective DP1 receptor agonist BW245C was completely inactive. We conclude that PGD2 and 15-deoxy-12,14-PGJ2 induce eosinophil infiltration into the lung through the DP2 receptor. The potent in vitro DP2 receptor agonist 15R-methyl-PGD2 is also very active in vivo and should be a useful tool in examining the role of this receptor.
Key words:
5-Oxo-ETE, CRTH2, DP2 receptor, Inflammation, Lungs, Prostaglandins
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