Prostaglandin D2 causes accumulation of eosinophils in the lumen of the dog trachea

Emery, D.L.; Djokic, T. D.; Graf, Paul; Nadel, Jay A.

doi:10.1152/jappl.1989.67.3.959

Cited by 69 publications

(41 citation statements)

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“…14 Furthermore, in dogs, PGD 2 caused a rapid reduction in circulating eosinophil levels, 15 whereas tracheal superfusion of PGD 2 in vivo induced the recruitment of eosinophils but not neutrophils into the superfusate. 16 It is unclear from the above studies whether the in vivo effects of PGD 2 are due to direct effects on eosinophils or are caused by the release of mediators from other cells. However, PGD 2 has been reported to directly stimulate calcium mobilization and LTC 4 release in vitro in human eosinophils.…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor

Monneret

Gravel

Diamond

et al. 2001

Blood

309

286

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Prostaglandin D 2 (PGD 2 ) is released following exposure of asthmatics to allergen and acts via the adenylyl cyclase-coupled receptor for PGD 2 (DP receptor). In this study, it is reported that human eosinophils possess this receptor, which would be expected to inhibit their activation. In contrast, it was found that prostaglandin D 2 is a potent stimulator of eosinophil chemotaxis, actin polymerization, CD11b expression, and Lselectin shedding. These responses are specific for eosinophils, as neutrophils display little or no response to prostaglandin D 2 . They were not due to interaction with receptors for other prostanoids, as prostaglandins E 2 and F 2␣ , U46619 (a thromboxane A 2 analogue), and carbaprostacyclin (a prostacyclin analogue) displayed little or no activity. Furthermore, they were not shared by the selective DP receptor agonist BW245C and were not prevented by the selective DP receptor antagonist BWA868C, indicating that they were not mediated by DP receptors. In contrast, the prostaglandin D 2 metabolite 13,14-dihydro-15-oxoprostaglandin D 2 induced eosinophil activation but did not stimulate DP receptor-mediated adenosine 3,5-cyclic monophosphate (cAMP) formation. These results indicate that in addition to the classic inhibitory DP 1 receptor, eosinophils possess a second, novel DP 2 receptor that is associated with PGD 2 -induced cell activation. These 2 receptors appear to interact to regulate eosinophil responses to PGD 2 , as blockade of DP 1 receptor-mediated cAMP production by BWA868C resulted in enhanced DP 2 receptor-mediated stimulation of CD11b expression. The balance between DP 1 and DP 2 receptors could determine the degree to which prostaglandin D 2 can activate eosinophils and may play a role in eosinophil recruitment in asthma. (Blood. 2001;98:1942-1948

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Section: Introductionmentioning

confidence: 99%

Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor

Monneret

Gravel

Diamond

et al. 2001

Blood

309

286

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“…Recent studies have shown that PGD 2 , a major cyclooxygenase (COX) 3 metabolite synthesized in activated mast cells and macrophages, is released during early and late asthmatic responses following allergen exposure (13,14), and acts as a potent chemoattractant of eosinophils in vitro (15,16) and in vivo (17,18). We have reported that COX-2 inhibitors, which stop the synthesis of PGD 2 in the lungs of allergen-sensitized and exposed guinea pigs, attenuated the accumulation of eosinophil in the airways (19).…”

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confidence: 99%

Cyclooxygenase-2/Prostaglandin D2/CRTH2 Pathway Mediates Double-Stranded RNA-Induced Enhancement of Allergic Airway Inflammation

Shiraishi

Asano

Niimi

et al. 2008

The Journal of Immunology

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Respiratory RNA viruses responsible for the common cold often worsen airway inflammation and bronchial responsiveness, two characteristic features of human asthma. We studied the effects of dsRNA, a nucleotide synthesized during viral replication, on airway inflammation and bronchial hyperresponsiveness in murine models of asthma. Intratracheal instillation of poly I:C, a synthetic dsRNA, increased the airway eosinophilia and enhanced bronchial hyperresponsiveness to methacholine in OVA-sensitized, exposed rats. These changes were associated with induction of cyclooxygenase-2 (COX-2) expression and COX-2-dependent PGD2 synthesis in the lungs, particularly in alveolar macrophages. The direct intratracheal instillation of PGD2 enhanced the eosinophilic inflammation in OVA-exposed animals, whereas pretreatment with a dual antagonist against the PGD2 receptor-(CRTH2) and the thromboxane A2 receptor, but not with a thromboxane A2 receptor-specific antagonist, nearly completely eliminated the dsRNA-induced worsening of airway inflammation and bronchial hyperresponsiveness. CRTH2-deficient mice had the same degree of allergen-induced airway eosinophilia as wild-type mice, but they did not exhibit a dsRNA-induced increase in eosinophil accumulation. Our data demonstrate that COX-2-dependent production of PGD2 followed by eosinophil recruitment into the airways via a CRTH2 receptor are the major pathogenetic factors responsible for the dsRNA-induced enhancement of airway inflammation and responsiveness.

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“…PGD 2 binds to and activates two G-protein-coupled receptors, DP1 and CRTH2 (chemoattractant receptor-homologous molecule expressed on Th type 2 cells), also known as DP2. Within the immune system, DP1 activation regulates human and murine dendritic cell migration (9), whereas CRTH2͞DP2 is expressed on type 2 lymphocytes (10), eosinophils (11), and basophils (12), where it mediates eosinophil chemotaxis and is currently implicated as a central player in promoting Th2-related allergic inflammation (13). Although 15d-PGJ 2 was identified as a high-affinity natural ligand for peroxisome proliferator-activated receptor (PPAR)␥, it is now thought to exert its effects through PPAR␥-dependent and -independent mechanisms, resulting in the suppression of various proinflammatory signaling pathways (2).…”

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confidence: 99%

Essential role for hematopoietic prostaglandin D2 synthase in the control of delayed type hypersensitivity

Trivedi

Newson²,

Rajakariar³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

122

109

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Hematopoietic prostaglandin D2 synthase (hPGD2S) metabolizes cyclooxygenase-derived prostaglandin (PG) H2 to PGD2, which is dehydrated to cyclopentenone PGs, including 15-deoxy-⌬ 12,14 -PGJ2 (15d-PGJ2). PGD2 acts through two receptors (DP1 and DP2͞CRTH2), whereas 15d-PGJ2 can activate peroxisome proliferator-activated receptors or inhibit a range of proinflammatory signaling pathways, including NF-B. Despite eliciting asthmatic and allergic reactions through the generation of PGD2, it is not known what role hPGD2S plays in T helper (Th)1-driven adaptive immunity. To investigate this question, the severity and duration of a delayed type hypersensitivity reaction was examined in hPGD2S knockout and transgenic mice. Compared with their respective controls, knockouts displayed a more severe inflammatory response that failed to resolve, characterized histologically as persistent acute inflammation, whereas transgenic mice had little detectable inflammation. Lymphocytes isolated from inguinal lymph nodes of hPGD2S ؊/؊ animals showed hyperproliferation and increased IL-2 synthesis effects that were rescued by 15d-PGJ2, but not PGD2, working through either of its receptors. Crucially, 15d-PGJ2 exerted its suppressive effects through the inhibition of NF-B activation and not through peroxisome proliferator-activated receptor signaling. In contrast, lymph node cultures from transgenics proliferated more slowly and synthesized significantly less IL-2 than controls. Therefore, contrary to its role in driving Th2-like responses, this report shows that hPGD2S may act as an internal braking signal essential for bringing about the resolution of Th1-driven delayed type hypersensitivity reactions. Consequently, hPGD2S-derived cyclopentenone PGs may protect against inflammatory diseases, where T lymphocytes play a pathogenic role, as in rheumatoid arthritis, atopic eczema, and chronic rejection.eicosanoids ͉ inflammation ͉ nonsteroidal antiinflammatory drugs ͉ resolution

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Prostaglandin D2 causes accumulation of eosinophils in the lumen of the dog trachea

Cited by 69 publications

References 0 publications

Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor

Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor

Cyclooxygenase-2/Prostaglandin D2/CRTH2 Pathway Mediates Double-Stranded RNA-Induced Enhancement of Allergic Airway Inflammation

Essential role for hematopoietic prostaglandin D2 synthase in the control of delayed type hypersensitivity

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