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Effects of prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats.
J Pharmacol Exp Ther. 2005 Apr; 313(1):64-9.JP

Abstract

Prostaglandin (PG) D2 is an arachidonic acid metabolite that is released by allergen-stimulated mast cells. It is a potent in vitro chemoattractant for human eosinophils, acting through the DP2 receptor/chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Furthermore, there is in vivo evidence that PGD2 contributes to allergen-induced pulmonary eosinophilia via its classic DP1 receptor. The PGD2-derived product 15-deoxy-Delta12,14-PGJ2 is widely used as a peroxisome proliferator-activated receptor gamma agonist and has been shown to have anti-inflammatory properties. However, this substance can also activate eosinophils in vitro through the DP2 receptor. The objectives of the present study were to determine whether PGD2 and 15-deoxy-Delta12,14-PGJ2 can induce pulmonary eosinophilia, and, if so, to examine the abilities of selective DP1 and DP2 receptor agonists to induce this response. Brown Norway rats were treated by intratracheal instillation of PGs. Vehicle and 5-oxo-6,8,11,14-eicosatetraenoic acid were used as negative and positive controls, respectively. Lung eosinophils were identified by immunostaining of lung sections with an antibody to major basic protein. Both PGD2 and 15-deoxy-Delta12,14-PGJ2 induced robust eosinophilic responses that were apparent by 12 h and persisted for at least 48 h. Two selective DP2 receptor agonists, 15R-methyl-PGD2 and 13-14-dihydro-15-keto-PGD2, induced similar responses, the former being more potent than PGD2, whereas the latter was less potent. The selective DP1 receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] was completely inactive. We conclude that PGD2 and 15-deoxy-Delta12,14-PGJ2 induce eosinophil infiltration into the lungs through the DP2 receptor. The potent in vitro DP2 receptor agonist 15R-methyl-PGD2 is also very active in vivo and should be a useful tool in examining the role of this receptor.

Authors+Show Affiliations

Meakins-Christie Laboratories, McGill University, 3626 St. Urbain St., Montreal, QC, Canada H2X 2P2.No 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
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15590767

Citation

Almishri, Wagdi, et al. "Effects of Prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and Selective DP1 and DP2 Receptor Agonists On Pulmonary Infiltration of Eosinophils in Brown Norway Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 313, no. 1, 2005, pp. 64-9.
Almishri W, Cossette C, Rokach J, et al. Effects of prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats. J Pharmacol Exp Ther. 2005;313(1):64-9.
Almishri, W., Cossette, C., Rokach, J., Martin, J. G., Hamid, Q., & Powell, W. S. (2005). Effects of prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats. The Journal of Pharmacology and Experimental Therapeutics, 313(1), 64-9.
Almishri W, et al. Effects of Prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and Selective DP1 and DP2 Receptor Agonists On Pulmonary Infiltration of Eosinophils in Brown Norway Rats. J Pharmacol Exp Ther. 2005;313(1):64-9. PubMed PMID: 15590767.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of prostaglandin D2, 15-deoxy-Delta12,14-prostaglandin J2, and selective DP1 and DP2 receptor agonists on pulmonary infiltration of eosinophils in Brown Norway rats. AU - Almishri,Wagdi, AU - Cossette,Chantal, AU - Rokach,Joshua, AU - Martin,James G, AU - Hamid,Qutayba, AU - Powell,William S, Y1 - 2004/12/08/ PY - 2004/12/14/pubmed PY - 2005/5/20/medline PY - 2004/12/14/entrez SP - 64 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 313 IS - 1 N2 - Prostaglandin (PG) D2 is an arachidonic acid metabolite that is released by allergen-stimulated mast cells. It is a potent in vitro chemoattractant for human eosinophils, acting through the DP2 receptor/chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). Furthermore, there is in vivo evidence that PGD2 contributes to allergen-induced pulmonary eosinophilia via its classic DP1 receptor. The PGD2-derived product 15-deoxy-Delta12,14-PGJ2 is widely used as a peroxisome proliferator-activated receptor gamma agonist and has been shown to have anti-inflammatory properties. However, this substance can also activate eosinophils in vitro through the DP2 receptor. The objectives of the present study were to determine whether PGD2 and 15-deoxy-Delta12,14-PGJ2 can induce pulmonary eosinophilia, and, if so, to examine the abilities of selective DP1 and DP2 receptor agonists to induce this response. Brown Norway rats were treated by intratracheal instillation of PGs. Vehicle and 5-oxo-6,8,11,14-eicosatetraenoic acid were used as negative and positive controls, respectively. Lung eosinophils were identified by immunostaining of lung sections with an antibody to major basic protein. Both PGD2 and 15-deoxy-Delta12,14-PGJ2 induced robust eosinophilic responses that were apparent by 12 h and persisted for at least 48 h. Two selective DP2 receptor agonists, 15R-methyl-PGD2 and 13-14-dihydro-15-keto-PGD2, induced similar responses, the former being more potent than PGD2, whereas the latter was less potent. The selective DP1 receptor agonist BW245C [(4S)-(3-[(3R,S)-3-cyclohexyl-3-hydroxypropyl]-2,5-dioxo)-4-imidazolidineheptanoic acid] was completely inactive. We conclude that PGD2 and 15-deoxy-Delta12,14-PGJ2 induce eosinophil infiltration into the lungs through the DP2 receptor. The potent in vitro DP2 receptor agonist 15R-methyl-PGD2 is also very active in vivo and should be a useful tool in examining the role of this receptor. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/15590767/Effects_of_prostaglandin_D2_15_deoxy_Delta1214_prostaglandin_J2_and_selective_DP1_and_DP2_receptor_agonists_on_pulmonary_infiltration_of_eosinophils_in_Brown_Norway_rats_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=15590767 DB - PRIME DP - Unbound Medicine ER -