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

被引:20
作者
Boehme, Stefen A. [1 ]
Franz-Bacon, Karin [1 ]
Chen, Edward P. [1 ]
Ly, Tai Wei [1 ]
Kawakami, Yuko [2 ]
Bacon, Kevin B. [1 ]
机构
[1] Actimis Pharmaceut Inc, San Diego, CA 92121 USA
[2] La Jolla Inst Allergy & Immunol, La Jolla, CA USA
关键词
allergy; chemotaxis; inflammation; prostaglandin D-2; FC-EPSILON-RI; AFFINITY IGE RECEPTOR; PROSTAGLANDIN D-2; EOSINOPHIL MIGRATION; IN-VITRO; ACTIVATION; CRTH2; DEGRANULATION; DP; INFLAMMATION;
D O I
10.1093/intimm/dxp031
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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) D-2. We demonstrate that primary murine bone marrow-derived mast cells (BMMCs) express the PGD(2) receptor; chemoattractant receptor-homologous molecule expressed on T-h class 2 cells (CRT(h)2). Activation of CRT(h)2 on BMMC by PGD(2) or the CRT(h)2-specific agonist, 13,14-dihydro-15-keto-prostaglandin D-2 (DK-PGD(2)), 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 CRT(h)2, Compound A. Activation of CRT(h)2 on BMMC also resulted in the up-regulation of CD23 and CD30 on the cell surface, as well as CD62L shedding. Finally, PGD(2) and DK-PGD(2) induced the migration of BMMC in vitro and in vivo in response to an intra-dermal DK-PGD(2) injection. Both these processes were inhibited by the CRT(h)2 antagonist. These results raise the possibility that the functional consequences of the PGD(2)-CRT(h)2 interaction on mast cells may be relevant in allergic inflammation.
引用
收藏
页码:621 / 632
页数:12
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