Delta 12-prostaglandin J2, a plasma metabolite of prostaglandin D2, causes eosinophil mobilization from the bone marrow and primes eosinophils for chemotaxis.
PGD(2), 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, PGD(2) is rapidly transformed into its major metabolite delta(12)-PGJ(2), the effect of which on eosinophil migration has not yet been characterized. In this study we found that delta(12)-PGJ(2) was a highly effective chemoattractant and inducer of respiratory burst in human eosinophils, with the same efficacy as PGD(2), PGJ(2), or 15-deoxy-delta(12,14)-PGJ(2). Moreover, pretreatment of eosinophils with delta(12)-PGJ(2) markedly enhanced the chemotactic response to eotaxin, and in this respect delta(12)-PGJ(2) was more effective than PGD(2). delta(12)-PGJ(2)-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 delta(12)-PGJ(2) signaled through the same receptor, CRTH2, as PGD(2). Finally, delta(12)-PGJ(2) was able to mobilize mature eosinophils from the bone marrow of the guinea pig isolated perfused hind limb. Given that delta(12)-PGJ(2) is present in the systemic circulation at relevant levels, a role for this PGD(2) metabolite in eosinophil release from the bone marrow and in driving eosinophil recruitment to sites of inflammation appears conceivable.
Heinemann
Akos
A
Department of Experimental and Clinical Pharmacology, Karl Franzens University, Graz, Austria. akos.heinemann@uni-graz.at
Schuligoi
Rufina
R
Sabroe
Ian
I
Hartnell
Adele
A
Peskar
Bernhard A
BA
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D001491:Basophils / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005260:Female; D005456:Fluorescent Dyes / Q000494:pharmacology; D006168:Guinea Pigs; D006614:Hindlimb; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D008297:Male; D010477:Perfusion; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis; D015230:Prostaglandin D2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000502:physiology*; D016897:Respiratory Burst / Q000187:drug effects / Q000502:physiology; D060149:Tetraspanin 30; D014966:Xanthenes / Q000494:pharmacology
D000814:Aniline Compounds; D015703:Antigens, CD; C554586:CD63 protein, human; D005456:Fluorescent Dyes; D018836:Inflammation Mediators; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D014966:Xanthenes; C059715:Fluo-3; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; D015230:Prostaglandin D2; D002118:Calcium