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Prostaglandin H2 induces the migration of human eosinophils through the chemoattractant receptor homologous molecule of Th2 cells, CRTH2.
J Leukoc Biol. 2009 Jan; 85(1):136-45.JL

Abstract

The major mast cell product PGD2 is released during the allergic response and stimulates the chemotaxis of eosinophils, basophils, and Th2-type T lymphocytes. The chemoattractant receptor homologous molecule of Th2 cells (CRTH2) has been shown to mediate the chemotactic effect of PGD2. PGH2 is the common precursor of all PGs and is produced by several cells that express cyclooxygenases. In this study, we show that PGH2 selectively stimulates human peripheral blood eosinophils and basophils but not neutrophils, and this effect is prevented by the CRTH2 receptor antagonist (+)-3-[[(4-fluorophenyl)sulfonyl] methyl amino]-1,2,3,4-tetrahydro-9H-carbazole-9-acetic acid (Cay10471) but not by the hematopoietic PGD synthase inhibitor 4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)-propyl]piperidine (HQL79). In chemotaxis assays, eosinophils showed a pronounced migratory response toward PGH2, but eosinophil degranulation was inhibited by PGH2. Moreover, collagen-induced platelet aggregation was inhibited by PGH2 in platelet-rich plasma, which was abrogated in the presence of the D-type prostanoid (DP) receptor antagonist 3-[(2-cyclohexyl-2-hydroxyethyl)amino]-2,5-dioxo-1-(phenylmethyl)-4-imidazolidine-heptanoic acid (BWA868c). Each of these effects of PGH2 was enhanced in the presence of plasma and/or albumin. In eosinophils, PGH2-induced calcium ion (Ca2+) flux was subject to homologous desensitization with PGD2. Human embryo kidney (HEK)293 cells transfected with human CRTH2 or DP likewise responded with Ca2+ flux, and untransfected HEK293 cells showed no response. These data indicate that PGH2 causes activation of the PGD2 receptors CRTH2 and DP via a dual mechanism: by interacting directly with the receptors and/or by giving rise to PGD2 after catalytic conversion by plasma proteins.

Authors+Show Affiliations

Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Universitaetsplatz 4. A-8010 Graz, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18835884

Citation

Schuligoi, Rufina, et al. "Prostaglandin H2 Induces the Migration of Human Eosinophils Through the Chemoattractant Receptor Homologous Molecule of Th2 Cells, CRTH2." Journal of Leukocyte Biology, vol. 85, no. 1, 2009, pp. 136-45.
Schuligoi R, Sedej M, Waldhoer M, et al. Prostaglandin H2 induces the migration of human eosinophils through the chemoattractant receptor homologous molecule of Th2 cells, CRTH2. J Leukoc Biol. 2009;85(1):136-45.
Schuligoi, R., Sedej, M., Waldhoer, M., Vukoja, A., Sturm, E. M., Lippe, I. T., Peskar, B. A., & Heinemann, A. (2009). Prostaglandin H2 induces the migration of human eosinophils through the chemoattractant receptor homologous molecule of Th2 cells, CRTH2. Journal of Leukocyte Biology, 85(1), 136-45. https://doi.org/10.1189/jlb.0608387
Schuligoi R, et al. Prostaglandin H2 Induces the Migration of Human Eosinophils Through the Chemoattractant Receptor Homologous Molecule of Th2 Cells, CRTH2. J Leukoc Biol. 2009;85(1):136-45. PubMed PMID: 18835884.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prostaglandin H2 induces the migration of human eosinophils through the chemoattractant receptor homologous molecule of Th2 cells, CRTH2. AU - Schuligoi,Rufina, AU - Sedej,Miriam, AU - Waldhoer,Maria, AU - Vukoja,Anela, AU - Sturm,Eva M, AU - Lippe,Irmgard T, AU - Peskar,Bernhard A, AU - Heinemann,Akos, Y1 - 2008/10/03/ PY - 2008/10/7/pubmed PY - 2009/4/3/medline PY - 2008/10/7/entrez SP - 136 EP - 45 JF - Journal of leukocyte biology JO - J Leukoc Biol VL - 85 IS - 1 N2 - The major mast cell product PGD2 is released during the allergic response and stimulates the chemotaxis of eosinophils, basophils, and Th2-type T lymphocytes. The chemoattractant receptor homologous molecule of Th2 cells (CRTH2) has been shown to mediate the chemotactic effect of PGD2. PGH2 is the common precursor of all PGs and is produced by several cells that express cyclooxygenases. In this study, we show that PGH2 selectively stimulates human peripheral blood eosinophils and basophils but not neutrophils, and this effect is prevented by the CRTH2 receptor antagonist (+)-3-[[(4-fluorophenyl)sulfonyl] methyl amino]-1,2,3,4-tetrahydro-9H-carbazole-9-acetic acid (Cay10471) but not by the hematopoietic PGD synthase inhibitor 4-benzhydryloxy-1-[3-(1H-tetrazol-5-yl)-propyl]piperidine (HQL79). In chemotaxis assays, eosinophils showed a pronounced migratory response toward PGH2, but eosinophil degranulation was inhibited by PGH2. Moreover, collagen-induced platelet aggregation was inhibited by PGH2 in platelet-rich plasma, which was abrogated in the presence of the D-type prostanoid (DP) receptor antagonist 3-[(2-cyclohexyl-2-hydroxyethyl)amino]-2,5-dioxo-1-(phenylmethyl)-4-imidazolidine-heptanoic acid (BWA868c). Each of these effects of PGH2 was enhanced in the presence of plasma and/or albumin. In eosinophils, PGH2-induced calcium ion (Ca2+) flux was subject to homologous desensitization with PGD2. Human embryo kidney (HEK)293 cells transfected with human CRTH2 or DP likewise responded with Ca2+ flux, and untransfected HEK293 cells showed no response. These data indicate that PGH2 causes activation of the PGD2 receptors CRTH2 and DP via a dual mechanism: by interacting directly with the receptors and/or by giving rise to PGD2 after catalytic conversion by plasma proteins. SN - 0741-5400 UR - https://www.unboundmedicine.com/medline/citation/18835884/Prostaglandin_H2_induces_the_migration_of_human_eosinophils_through_the_chemoattractant_receptor_homologous_molecule_of_Th2_cells_CRTH2_ L2 - https://doi.org/10.1189/jlb.0608387 DB - PRIME DP - Unbound Medicine ER -