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. doi: 10.1111/j.1365-2222.2004.02027.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basophils / physiology*
  • CD11b Antigen / analysis
  • Calcium / metabolism
  • Cell Movement
  • Cell Survival
  • Cells, Cultured
  • Chemotaxis
  • Histamine Release
  • Humans
  • Hydantoins / pharmacology
  • Hypersensitivity / immunology*
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / metabolism
  • Prostaglandin D2 / pharmacology
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism*
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Receptors, Prostaglandin / genetics
  • Receptors, Prostaglandin / immunology*
  • Receptors, Prostaglandin / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Th2 Cells / metabolism*


  • CD11b Antigen
  • Hydantoins
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • 13,14-dihydro-15-ketoprostaglandin D2
  • BW 245C
  • Prostaglandin D2
  • Calcium
  • prostaglandin D2 receptor