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Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor-homologous molecule expressed on Th2 cells/DP2.
Clin Exp Allergy. 2004 Aug; 34(8):1283-90.CE

Abstract

BACKGROUND

Both prostaglandin (PG) D receptor (DP) and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells)/DP2 are high-affinity receptors for PGD2. Previous studies have demonstrated that PGD2 enhances releasability and induces CRTH2/DP2-mediated migration in human basophils, but the precise effects of PGD2 on basophils as well as receptor usage have not been fully clarified.

OBJECTIVE

We comprehensively explored the roles of DP and CRTH2/DP2 in basophil functions by using selective agonists and antagonists for each receptor.

METHODS

DP and CRTH2/DP2 transcripts were quantified by real-time PCR. We studied the effects of selective agonists (DP: BW245C; CRTH2/DP2: 13,14-dihydro-15-keto (DK)-PGD2) and/or antagonists (DP: BWA868C; CRTH2/DP2: ramatroban) on Ca2+ mobilization, migration, degranulation, CD11b expression and survival of human basophils.

RESULTS

Basophils expressed transcripts of both DP and CRTH2/DP2, but the levels of CRTH2/DP2 transcripts were ca. 100-fold higher compared with DP transcripts. Ca2+ influx was induced in basophils by either PGD2 or DK-PGD2/CRTH2 agonist but not by BW245C/DP agonist. Basophils treated with PGD2 were completely desensitized to subsequent stimulation with DK-PGD2, but not vice versa. DK-PGD2 as well as PGD2 up-regulated CD11b expression, induced migration and enhanced degranulation, and those effects were completely antagonized by ramatroban/CRTH2 antagonist. In contrast, BW245C/DP agonist exhibited an inhibitory effect on basophil migration and IgE-mediated degranulation, and the migration inhibitory effect was effectively antagonized by BWA868C/DP antagonist. On the other hand, while PGD2 significantly shortened the basophil life-span, neither DK-PGD2/CRTH2 agonist nor BW245C/DP agonist did.

CONCLUSION

CRTH2/DP2 is primarily responsible for the pro-inflammatory effects of PGD2 on human basophils, while DP introduces negative signals capable of antagonizing the effects of CRTH2/DP2 in these cells. The effects of PGD2 on longevity imply a mechanism(s) other than via DP or CRTH2/DP2. CRTH2/DP2 on basophils may afford opportunities for therapeutic targeting in allergic inflammation.

Authors+Show Affiliations

Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo 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

15298571

Citation

Yoshimura-Uchiyama, C, et al. "Differential Modulation of Human Basophil Functions Through Prostaglandin D2 Receptors DP and Chemoattractant Receptor-homologous Molecule Expressed On Th2 Cells/DP2." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 34, no. 8, 2004, pp. 1283-90.
Yoshimura-Uchiyama C, Iikura M, Yamaguchi M, et al. Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor-homologous molecule expressed on Th2 cells/DP2. Clin Exp Allergy. 2004;34(8):1283-90.
Yoshimura-Uchiyama, C., Iikura, M., Yamaguchi, M., Nagase, H., Ishii, A., Matsushima, K., Yamamoto, K., Shichijo, M., Bacon, K. B., & Hirai, K. (2004). Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor-homologous molecule expressed on Th2 cells/DP2. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 34(8), 1283-90.
Yoshimura-Uchiyama C, et al. Differential Modulation of Human Basophil Functions Through Prostaglandin D2 Receptors DP and Chemoattractant Receptor-homologous Molecule Expressed On Th2 Cells/DP2. Clin Exp Allergy. 2004;34(8):1283-90. PubMed PMID: 15298571.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential modulation of human basophil functions through prostaglandin D2 receptors DP and chemoattractant receptor-homologous molecule expressed on Th2 cells/DP2. AU - Yoshimura-Uchiyama,C, AU - Iikura,M, AU - Yamaguchi,M, AU - Nagase,H, AU - Ishii,A, AU - Matsushima,K, AU - Yamamoto,K, AU - Shichijo,M, AU - Bacon,K B, AU - Hirai,K, PY - 2004/8/10/pubmed PY - 2004/12/21/medline PY - 2004/8/10/entrez SP - 1283 EP - 90 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin Exp Allergy VL - 34 IS - 8 N2 - BACKGROUND: Both prostaglandin (PG) D receptor (DP) and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells)/DP2 are high-affinity receptors for PGD2. Previous studies have demonstrated that PGD2 enhances releasability and induces CRTH2/DP2-mediated migration in human basophils, but the precise effects of PGD2 on basophils as well as receptor usage have not been fully clarified. OBJECTIVE: We comprehensively explored the roles of DP and CRTH2/DP2 in basophil functions by using selective agonists and antagonists for each receptor. METHODS: DP and CRTH2/DP2 transcripts were quantified by real-time PCR. We studied the effects of selective agonists (DP: BW245C; CRTH2/DP2: 13,14-dihydro-15-keto (DK)-PGD2) and/or antagonists (DP: BWA868C; CRTH2/DP2: ramatroban) on Ca2+ mobilization, migration, degranulation, CD11b expression and survival of human basophils. RESULTS: Basophils expressed transcripts of both DP and CRTH2/DP2, but the levels of CRTH2/DP2 transcripts were ca. 100-fold higher compared with DP transcripts. Ca2+ influx was induced in basophils by either PGD2 or DK-PGD2/CRTH2 agonist but not by BW245C/DP agonist. Basophils treated with PGD2 were completely desensitized to subsequent stimulation with DK-PGD2, but not vice versa. DK-PGD2 as well as PGD2 up-regulated CD11b expression, induced migration and enhanced degranulation, and those effects were completely antagonized by ramatroban/CRTH2 antagonist. In contrast, BW245C/DP agonist exhibited an inhibitory effect on basophil migration and IgE-mediated degranulation, and the migration inhibitory effect was effectively antagonized by BWA868C/DP antagonist. On the other hand, while PGD2 significantly shortened the basophil life-span, neither DK-PGD2/CRTH2 agonist nor BW245C/DP agonist did. CONCLUSION: CRTH2/DP2 is primarily responsible for the pro-inflammatory effects of PGD2 on human basophils, while DP introduces negative signals capable of antagonizing the effects of CRTH2/DP2 in these cells. The effects of PGD2 on longevity imply a mechanism(s) other than via DP or CRTH2/DP2. CRTH2/DP2 on basophils may afford opportunities for therapeutic targeting in allergic inflammation. SN - 0954-7894 UR - https://www.unboundmedicine.com/medline/citation/15298571/Differential_modulation_of_human_basophil_functions_through_prostaglandin_D2_receptors_DP_and_chemoattractant_receptor_homologous_molecule_expressed_on_Th2_cells/DP2_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0954-7894&date=2004&volume=34&issue=8&spage=1283 DB - PRIME DP - Unbound Medicine ER -