9alpha,11beta-PGF2 and its stereoisomer PGF2alpha are novel agonists of the chemoattractant receptor, CRTH2.
CRTH2 is a recently described chemoattractant receptor for the prostaglandin, PGD(2), expressed by Th2 cells, eosinophils and basophils, and believed to play a role in allergic inflammation. Here we describe the potency of several PGD(2) metabolites at the receptor to induce cell migration and activation. We report for the first time that the PGD(2) metabolite, 9alpha,11beta-PGF(2), and its stereoisomer, PGF(2alpha), are CRTH2 agonists. 9alpha,11beta-PGF(2) is a major metabolite produced in vivo following allergen challenge, whilst PGF(2alpha) is generated independently of PGD synthetase, with implications for CRTH2 signalling in the presence or absence of PGD(2) production.
Sandig
Hilary
H
Leukocyte Biology Section, NHLI Division, Imperial College Faculty of Medicine, South Kensington, London SW7 2AZ, UK.
Andrew
David
D
Barnes
Ashley A
AA
Sabroe
Ian
I
Pease
James
J
D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D015237:Dinoprost / Q000737:chemistry / Q000378:metabolism*; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D010120:Oxytocics / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000819:agonists* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism
D010120:Oxytocics; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D015237:Dinoprost; C036293:prostaglandin D2 receptor