Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in leukocyte function.
Traditionally, PGD(2) has been considered to be a pro-inflammatory mediator, acting via classical PG receptors, such as the PGD(2) receptor (DP). PGD(2) is degraded rapidly in vitro and in vivo to a variety of metabolites, the majority of which were thought, until recently, to be physiologically inactive. Several "inactive" metabolites, particularly 15d-PGJ(2), have been shown to have wide-ranging effects on leukocytes and other cell types, however, and a potentially important anti-inflammatory role for PGD(2) has now been recognized, and the complexity of PGD(2) signaling is beginning to be elucidated. PGD(2) and its metabolites are biologically active over a broad concentration range, and, intriquingly, it appears that there are marked concentration-dependent variations in the consequences of signaling by these eicosanoids, which have the potential to exert pro- and anti-inflammatory effects. For example, the actions of PGD(2) can influence multiple stages in the life of the mature eosinophil, from causing its release from the bone marrow to inducing its recruitment and activation and, ultimately, regulating its apoptosis. This review is concerned with the diverse responses induced in leukocytes by PGD(2) and its metabolites and the signaling mechanisms which are thought to be responsible for them.
Sandig
Hilary
H
Department of Asthma, Allergy and Respiratory Science, King's College London, 5th Floor Thomas Guy House, Guy's Hospital, London, UK. Hilary.sandig@kcl.ac.uk
Pease
James E
JE
Sabroe
Ian
I
D000818:Animals; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008968:Molecular Conformation; D015230:Prostaglandin D2 / Q000737:chemistry / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013237:Stereoisomerism
D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor