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Prostaglandin D2 receptor D-type prostanoid receptor 2 mediates eosinophil trafficking into the esophagus.
Dis Esophagus. 2014 Aug; 27(6):601-6.DE

Abstract

Eosinophilic esophagitis is characterized by eosinophil-predominant inflammation in the esophagus. How eosinophils migrate and infiltrate into the esophagus, however, is less clear. Our previous study demonstrated that mast cell activation led to eosinophil infiltration in the esophagus. Prostaglandin D2 (PGD2) is an important mediator released from activated mast cells. The present study aims to determine whether PGD2 induces eosinophil infiltration into the esophagus via a d-type prostanoid receptor 2 (DP2) receptor-dependent mechanism. Using an in vivo guinea pig model, PGD2, d-type prostanoid receptor 1 (DP1) agonist, or DP2 agonist were injected into the esophagus. Esophageal tissues were removed 2 hours after injections and proceeded to either hematoxylin-eosin (HE) staining or immunofluorescent staining of eosinophil major basic protein (MBP) to compare each treatment-induced eosinophil infiltration in the esophagus. In a separate study, ovalbumin (OVA)-sensitized guinea pigs were pretreated with either DP2 or DP1 antagonists, followed by inhalation of OVA to induce mast cell activation. Esophageal tissues were then processed for immunofluorescent staining of MBP. PGD2 injection in the esophagus led to an increase of eosinophil infiltration in esophageal epithelium at the injection site as revealed by HE staining. Increased infiltration of eosinophils was further confirmed by the increased presence of MBP-labeled immunopositive (MBP-LI) cells in esophageal epithelium. Injection with DP2 agonist 15(R)-PGD2, but not DP1 agonist BW 245C, mimicked the PGD2-induced response. In OVA-sensitized animals, antigen inhalation increased MBP-LI cells in esophageal epithelium. Pretreatment with DP2 antagonist BAY-u3405, but not DP1 antagonist BW 868C, inhibited the antigen inhalation-induced increase of MBP-LI cells in esophageal epithelium. These data support the hypothesis that PGD2 induces eosinophil trafficking into the esophageal epithelium via a DP2-mediated pathway, suggesting a role of DP2 antagonist in the prevention of eosinophilic esophagitis.

Authors+Show Affiliations

Division of Gastroenterology, Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24165271

Citation

Zhang, S, et al. "Prostaglandin D2 Receptor D-type Prostanoid Receptor 2 Mediates Eosinophil Trafficking Into the Esophagus." Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus, vol. 27, no. 6, 2014, pp. 601-6.
Zhang S, Wu X, Yu S. Prostaglandin D2 receptor D-type prostanoid receptor 2 mediates eosinophil trafficking into the esophagus. Dis Esophagus. 2014;27(6):601-6.
Zhang, S., Wu, X., & Yu, S. (2014). Prostaglandin D2 receptor D-type prostanoid receptor 2 mediates eosinophil trafficking into the esophagus. Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus, 27(6), 601-6. https://doi.org/10.1111/dote.12118
Zhang S, Wu X, Yu S. Prostaglandin D2 Receptor D-type Prostanoid Receptor 2 Mediates Eosinophil Trafficking Into the Esophagus. Dis Esophagus. 2014;27(6):601-6. PubMed PMID: 24165271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prostaglandin D2 receptor D-type prostanoid receptor 2 mediates eosinophil trafficking into the esophagus. AU - Zhang,S, AU - Wu,X, AU - Yu,S, Y1 - 2013/10/25/ PY - 2013/10/30/entrez PY - 2013/10/30/pubmed PY - 2015/5/13/medline KW - eosinophilic esophagitis (EoE) KW - mast cell KW - prostaglandin D2 SP - 601 EP - 6 JF - Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus JO - Dis Esophagus VL - 27 IS - 6 N2 - Eosinophilic esophagitis is characterized by eosinophil-predominant inflammation in the esophagus. How eosinophils migrate and infiltrate into the esophagus, however, is less clear. Our previous study demonstrated that mast cell activation led to eosinophil infiltration in the esophagus. Prostaglandin D2 (PGD2) is an important mediator released from activated mast cells. The present study aims to determine whether PGD2 induces eosinophil infiltration into the esophagus via a d-type prostanoid receptor 2 (DP2) receptor-dependent mechanism. Using an in vivo guinea pig model, PGD2, d-type prostanoid receptor 1 (DP1) agonist, or DP2 agonist were injected into the esophagus. Esophageal tissues were removed 2 hours after injections and proceeded to either hematoxylin-eosin (HE) staining or immunofluorescent staining of eosinophil major basic protein (MBP) to compare each treatment-induced eosinophil infiltration in the esophagus. In a separate study, ovalbumin (OVA)-sensitized guinea pigs were pretreated with either DP2 or DP1 antagonists, followed by inhalation of OVA to induce mast cell activation. Esophageal tissues were then processed for immunofluorescent staining of MBP. PGD2 injection in the esophagus led to an increase of eosinophil infiltration in esophageal epithelium at the injection site as revealed by HE staining. Increased infiltration of eosinophils was further confirmed by the increased presence of MBP-labeled immunopositive (MBP-LI) cells in esophageal epithelium. Injection with DP2 agonist 15(R)-PGD2, but not DP1 agonist BW 245C, mimicked the PGD2-induced response. In OVA-sensitized animals, antigen inhalation increased MBP-LI cells in esophageal epithelium. Pretreatment with DP2 antagonist BAY-u3405, but not DP1 antagonist BW 868C, inhibited the antigen inhalation-induced increase of MBP-LI cells in esophageal epithelium. These data support the hypothesis that PGD2 induces eosinophil trafficking into the esophageal epithelium via a DP2-mediated pathway, suggesting a role of DP2 antagonist in the prevention of eosinophilic esophagitis. SN - 1442-2050 UR - https://www.unboundmedicine.com/medline/citation/24165271/Prostaglandin_D2_receptor_D_type_prostanoid_receptor_2_mediates_eosinophil_trafficking_into_the_esophagus_ L2 - https://academic.oup.com/dote/article-lookup/doi/10.1111/dote.12118 DB - PRIME DP - Unbound Medicine ER -