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International Immunology

Year: 2009  |  Volume: 21  |  Issue: 6  |  Page No.: 621 - 632

Murine bone marrow-derived mast cells express chemoattractant receptor-homologous molecule expressed on T-helper class 2 cells (CRTh2)

S. A Boehme, K Franz Bacon, E. P Chen, T. W Ly, Y Kawakami and K. B. Bacon

Abstract

Mast cells are bone marrow-derived effector cells that can initiate inflammatory responses to infectious organisms or allergens by releasing a multitude of pro-inflammatory factors including prostaglandin (PG) D2. We demonstrate that primary murine bone marrow-derived mast cells (BMMCs) express the PGD2 receptor; chemoattractant receptor-homologous molecule expressed on Th class 2 cells (CRTh2). Activation of CRTh2 on BMMC by PGD2 or the CRTh2-specific agonist, 13,14-dihydro-15-keto-prostaglandin D2 (DK-PGD2), resulted in signaling response including Ca2+ mobilization and phosphorylation of the p42/p44 extracellular signal-regulated kinases (ERKs) kinases. Phosphorylation of the ERKs could be blocked by pertussis toxin, as well as a small molecule antagonist of CRTh2, Compound A. Activation of CRTh2 on BMMC also resulted in the up-regulation of CD23 and CD30 on the cell surface, as well as CD62L shedding. Finally, PGD2 and DK-PGD2 induced the migration of BMMC in vitro and in vivo in response to an intra-dermal DK-PGD2 injection. Both these processes were inhibited by the CRTh2 antagonist. These results raise the possibility that the functional consequences of the PGD2–CRTh2 interaction on mast cells may be relevant in allergic inflammation.

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