The effect of prostaglandin D2 (PGD2) on circulating eosinophils

Marsden, Kate; Rao, P. S.; Cavanagh, Denis; Spaziani, Eric P.

doi:10.1016/0262-1746(84)90137-9

Cited by 10 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although Peskar & Brune already proposed in 1979 that PGD2 was the prevailing PG in acute inflammatory responses [ 14 ], its immune modulator mode of action still needed to be elucidated. In dogs, two studies indirectly suggested that PGD2 might be a chemoattractant for eosinophils, the first showing that intravenous PGD 2 caused a transient drop in circulating eosinophil numbers [ 15 ], and the second that intratracheal PGD2 caused intra-luminal eosinophil accumulation [ 16 ]. In 1990, Woodward et al described the ocular hypotensive effect of PGD 2 and the selective DP1 agonist BW245c in guinea pigs [ 17 ].…”

Section: Crth2 – History and Clinical Potentialmentioning

confidence: 99%

The therapeutic potential of CRTH2/DP2 beyond allergy and asthma

Jandl

Heinemann

2017

Prostaglandins & Other Lipid Mediators

View full text Add to dashboard Cite

Prostaglandin (PG) D has been in the focus of research for quite a long time, but its biological effects and its roles in human disease are still not fully characterized. When in 2001 a second major PGD receptor termed chemoattractant receptor homologue expressed on Th2 cells (CRTH2; alternative name DP2) was discovered, diverse investigations started to shed more light on the complex and often controversial actions of the prostaglandin. With various immunomodulating effects, such as induction of migration, activation, and cytokine release of leukocytes observed both in vivo and in vitro, CRTH2 has emerged as a promising target for the treatment of allergic diseases. However, with more and more research being performed on CRTH2, it has also become clear that its biological actions are far more diverse than expected at the beginning. In this review, we aim to summarize the roles that PGD - and CRTH2 in particular - might play in diseases of the central nervous system, kidney, intestine, lung, hair and skin, bone and cartilage, and in cancer. Based on current data we propose that blocking CRTH2 might be a potential therapeutic approach to numerous conditions beyond classical allergic diseases and asthma.

show abstract

Section: Crth2 – History and Clinical Potentialmentioning

confidence: 99%

The therapeutic potential of CRTH2/DP2 beyond allergy and asthma

Jandl

Heinemann

2017

Prostaglandins & Other Lipid Mediators

View full text Add to dashboard Cite

show abstract

“…13 The reduction in eosinophil recruitment is interesting in view of the key role played by these cells in the pathophysiology of asthma owing to their release of proinflammatory cytokines, bronchoconstrictor cysteinyl leukotrienes (LTs), degradative enzymes, and other factors. 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.…”

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

View full text Add to dashboard Cite

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

show abstract