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. PGD2 activity is principally mediated through two unique G protein-coupled receptors (GPCR), designated DP1 and DP2. These receptors exhibit overlapping binding profiles, yet their respective agonists elicit generally distinctive responses. Additional to DP receptors, the PGD, metabolite 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) binds the nuclear peroxisome proliferator-activated receptor gamma (PPAR gamma) and has the facility to initiate a variety of anti-inflammatory phenotypes either through or independent of PPAR gamma association. This review highlights the collective relevance of PGD2 and its respective synthases, receptors, and metabolites in immunopathologic responses. (c) 2005 Elsevier B.V. All rights reserved.