Positioning prostanoids of the D and J series in the immunopathogenic scheme

Prostaglandin D(2) (PGD(2)) is produced by a variety of immune and non-hematopoietic cells and appears to function in both an inflammatory and homeostatic capacity. Two genetically distinct PGD(2)-synthesizing enzymes have been identified to date, including hematopoietic- and lipocalin-type PGD synthases (H-PGDS and L-PGDS, respectively). Though the inter-species expression profiles of these two enzymes vary widely, H-PGDS is generally localized to the cytosolic aspect of immune and inflammatory cells, whereas L-PGDS is more resigned to tissue-based expression. PGD(2) activity is principally mediated through two unique G protein-coupled receptors (GPCR), designated DP(1) and DP(2). These receptors exhibit overlapping binding profiles, yet their respective agonists elicit generally distinctive responses. Additional to DP receptors, the PGD(2) metabolite 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) binds the nuclear peroxisome proliferator-activated receptor gamma (PPARgamma) and has the facility to initiate a variety of anti-inflammatory phenotypes either through or independent of PPARgamma association. This review highlights the collective relevance of PGD(2) and its respective synthases, receptors, and metabolites in immunopathologic responses.