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12-Prostaglandin J2, a Plasma Metabolite of Prostaglandin D2, Causes Eosinophil Mobilization from the Bone Marrow and Primes Eosinophils for Chemotaxis1
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* Department of Experimental and Clinical Pharmacology, Karl Franzens University, Graz, Austria;
Leukocyte Biology Section, Biomedical Sciences Division, Imperial College Faculty of Medicine, Imperial College of Science, Technology, and Medicine, South Kensington, London, United Kingdom; and
Section of Functional Genomics, Division of Genomic Medicine, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom
PGD2, a major mast cell mediator, is a potent eosinophil chemoattractant and is thought to be involved in eosinophil recruitment to sites of allergic inflammation. In plasma, PGD2 is rapidly transformed into its major metabolite 
12-PGJ2, the effect of which on eosinophil migration has not yet been characterized. In this study we found that 12-PGJ2 was a highly effective chemoattractant and inducer of respiratory burst in human eosinophils, with the same efficacy as PGD2, PGJ2, or 15-deoxy-12,14-PGJ2. Moreover, pretreatment of eosinophils with 12-PGJ2 markedly enhanced the chemotactic response to eotaxin, and in this respect 12-PGJ2 was more effective than PGD2. 12-PGJ2-induced facilitation of eosinophil migration toward eotaxin was not altered by specific inhibitors of intracellular signaling pathways relevant to the chemotactic response, phosphatidylinositol 3-kinase (LY-294002), mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (U-0126), or p38 mitogen-activated protein kinase (SB-202190). Desensitization studies using calcium flux suggested that 12-PGJ2 signaled through the same receptor, CRTH2, as PGD2. Finally, 12-PGJ2 was able to mobilize mature eosinophils from the bone marrow of the guinea pig isolated perfused hind limb. Given that 12-PGJ2 is present in the systemic circulation at relevant levels, a role for this PGD2 metabolite in eosinophil release from the bone marrow and in driving eosinophil recruitment to sites of inflammation appears conceivable.
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