The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking

Petra Schratl; Julia F Royer; Evi Kostenis; Trond Ulven; Eva M Sturm; Maria Waldhoer; Gerald Hoefler; Rufina Schuligoi; Irmgard Th Lippe; Bernhard A Peskar; Akos Heinemann

The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking

Petra Schratl, Julia F Royer, Evi Kostenis, Trond Ulven, Eva M Sturm, Maria Waldhoer, Gerald Hoefler, Rufina Schuligoi, Irmgard Th Lippe, Bernhard A Peskar, Akos Heinemann

56 Citationer (Scopus)

Abstract

Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role of DP has remained unclear. We report in this study that, in addition to CRTH2, the DP receptor plays an important role in eosinophil trafficking. First, we investigated the release of eosinophils from bone marrow using the in situ perfused guinea pig hind limb preparation. PGD2 induced the rapid release of eosinophils from bone marrow and this effect was inhibited by either the DP receptor antagonist BWA868c or the CRTH2 receptor antagonist ramatroban. In contrast, BWA868c did not inhibit the release of bone marrow eosinophils when this was induced by the CRTH2-selective agonist 13,14-dihydro-15-keto-PGD2. In additional experiments, we isolated bone marrow eosinophils from the femoral cavity and found that these cells migrated toward PGD2. We also observed that BWA868c inhibited this response to a similar extent as ramatroban. Finally, using immunohistochemistry we could demonstrate that eosinophils in human bone marrow specimens expressed DP and CRTH2 receptors at similar levels. Eosinophils isolated from human peripheral blood likewise expressed DP receptor protein but at lower levels than CRTH2. In agreement with this, the chemotaxis of human peripheral blood eosinophils was inhibited both by BWA868c and ramatroban. These findings suggest that DP receptors comediate with CRTH2 the mobilization of eosinophils from bone marrow and their chemotaxis, which might provide the rationale for DP antagonists in the treatment of allergic disease Udgivelsesdato: 2007-Oct-1

Originalsprog	Engelsk
Tidsskrift	Journal of Immunology
Vol/bind	179
Udgave nummer	7
Sider (fra-til)	4792-4799
Antal sider	8
ISSN	0022-1767
Status	Udgivet - 1 okt. 2007

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title = "The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking",

abstract = "Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role of DP has remained unclear. We report in this study that, in addition to CRTH2, the DP receptor plays an important role in eosinophil trafficking. First, we investigated the release of eosinophils from bone marrow using the in situ perfused guinea pig hind limb preparation. PGD2 induced the rapid release of eosinophils from bone marrow and this effect was inhibited by either the DP receptor antagonist BWA868c or the CRTH2 receptor antagonist ramatroban. In contrast, BWA868c did not inhibit the release of bone marrow eosinophils when this was induced by the CRTH2-selective agonist 13,14-dihydro-15-keto-PGD2. In additional experiments, we isolated bone marrow eosinophils from the femoral cavity and found that these cells migrated toward PGD2. We also observed that BWA868c inhibited this response to a similar extent as ramatroban. Finally, using immunohistochemistry we could demonstrate that eosinophils in human bone marrow specimens expressed DP and CRTH2 receptors at similar levels. Eosinophils isolated from human peripheral blood likewise expressed DP receptor protein but at lower levels than CRTH2. In agreement with this, the chemotaxis of human peripheral blood eosinophils was inhibited both by BWA868c and ramatroban. These findings suggest that DP receptors comediate with CRTH2 the mobilization of eosinophils from bone marrow and their chemotaxis, which might provide the rationale for DP antagonists in the treatment of allergic disease Udgivelsesdato: 2007-Oct-1",

keywords = "Animals, Bone Marrow, Cells, Cultured, Chemotaxis, Eosinophils, Femur, Guinea Pigs, Humans, Ligands, Prostaglandins D, Receptors, Immunologic, Receptors, Prostaglandin",

author = "Petra Schratl and Royer, {Julia F} and Evi Kostenis and Trond Ulven and Sturm, {Eva M} and Maria Waldhoer and Gerald Hoefler and Rufina Schuligoi and Lippe, {Irmgard Th} and Peskar, {Bernhard A} and Akos Heinemann",

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T1 - The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking

AU - Schratl, Petra

AU - Royer, Julia F

AU - Kostenis, Evi

AU - Ulven, Trond

AU - Sturm, Eva M

AU - Waldhoer, Maria

AU - Hoefler, Gerald

AU - Schuligoi, Rufina

AU - Lippe, Irmgard Th

AU - Peskar, Bernhard A

AU - Heinemann, Akos

PY - 2007/10/1

Y1 - 2007/10/1

N2 - Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role of DP has remained unclear. We report in this study that, in addition to CRTH2, the DP receptor plays an important role in eosinophil trafficking. First, we investigated the release of eosinophils from bone marrow using the in situ perfused guinea pig hind limb preparation. PGD2 induced the rapid release of eosinophils from bone marrow and this effect was inhibited by either the DP receptor antagonist BWA868c or the CRTH2 receptor antagonist ramatroban. In contrast, BWA868c did not inhibit the release of bone marrow eosinophils when this was induced by the CRTH2-selective agonist 13,14-dihydro-15-keto-PGD2. In additional experiments, we isolated bone marrow eosinophils from the femoral cavity and found that these cells migrated toward PGD2. We also observed that BWA868c inhibited this response to a similar extent as ramatroban. Finally, using immunohistochemistry we could demonstrate that eosinophils in human bone marrow specimens expressed DP and CRTH2 receptors at similar levels. Eosinophils isolated from human peripheral blood likewise expressed DP receptor protein but at lower levels than CRTH2. In agreement with this, the chemotaxis of human peripheral blood eosinophils was inhibited both by BWA868c and ramatroban. These findings suggest that DP receptors comediate with CRTH2 the mobilization of eosinophils from bone marrow and their chemotaxis, which might provide the rationale for DP antagonists in the treatment of allergic disease Udgivelsesdato: 2007-Oct-1

AB - Prostaglandin (PG) D2 is a major mast cell product that acts via two receptors, the D-type prostanoid (DP) and the chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) receptors. Whereas CRTH2 mediates the chemotaxis of eosinophils, basophils, and Th2 lymphocytes, the role of DP has remained unclear. We report in this study that, in addition to CRTH2, the DP receptor plays an important role in eosinophil trafficking. First, we investigated the release of eosinophils from bone marrow using the in situ perfused guinea pig hind limb preparation. PGD2 induced the rapid release of eosinophils from bone marrow and this effect was inhibited by either the DP receptor antagonist BWA868c or the CRTH2 receptor antagonist ramatroban. In contrast, BWA868c did not inhibit the release of bone marrow eosinophils when this was induced by the CRTH2-selective agonist 13,14-dihydro-15-keto-PGD2. In additional experiments, we isolated bone marrow eosinophils from the femoral cavity and found that these cells migrated toward PGD2. We also observed that BWA868c inhibited this response to a similar extent as ramatroban. Finally, using immunohistochemistry we could demonstrate that eosinophils in human bone marrow specimens expressed DP and CRTH2 receptors at similar levels. Eosinophils isolated from human peripheral blood likewise expressed DP receptor protein but at lower levels than CRTH2. In agreement with this, the chemotaxis of human peripheral blood eosinophils was inhibited both by BWA868c and ramatroban. These findings suggest that DP receptors comediate with CRTH2 the mobilization of eosinophils from bone marrow and their chemotaxis, which might provide the rationale for DP antagonists in the treatment of allergic disease Udgivelsesdato: 2007-Oct-1

KW - Animals

KW - Bone Marrow

KW - Cells, Cultured

KW - Chemotaxis

KW - Eosinophils

KW - Femur

KW - Guinea Pigs

KW - Humans

KW - Ligands

KW - Prostaglandins D

KW - Receptors, Immunologic

KW - Receptors, Prostaglandin

M3 - Journal article

SN - 0022-1767

VL - 179

SP - 4792

EP - 4799

JO - Journal of Immunology

JF - Journal of Immunology

IS - 7

ER -

The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking

Abstract

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