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Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Schratl, P; Royer, JF; Kostenis, E; Ulven, T; Sturm, EM; Waldhoer, M; Hoefler, G; Schuligoi, R; Lippe, IT; Peskar, BA; Heinemann, A.
The role of the prostaglandin D2 receptor, DP, in eosinophil trafficking.
J Immunol. 2007; 179(7):4792-4799
Doi: 10.4049/jimmunol.179.7.4792
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- Führende Autor*innen der Med Uni Graz
- Heinemann Akos
- Luschnig Petra
- Co-Autor*innen der Med Uni Graz
- Böhm Eva
- Höfler Gerald
- Lippe Irmgard Theresia
- Peskar Bernhard
- Royer Julia
- Schuligoi Rufina
- Waldhoer Maria
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Bone Marrow -
- Cells, Cultured -
- Chemotaxis - drug effects
- Eosinophils - cytology
- Femur - cytology
- Guinea Pigs - cytology
- Humans - cytology
- Ligands - cytology
- Prostaglandins D - metabolism
- Receptors, Immunologic - genetics
- Receptors, Prostaglandin - genetics