Murine bone marrow-derived mast cells express chemoattractant receptor-homologous molecule expressed on T-helper class 2 cells (CRTh2).
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 Ca(2+) 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.
Actimis Pharmaceuticals, Inc., 10835 Road to the Cure, San Diego, CA 92121, USA. sboehme@actimis.com
Stefen A
SA
Boehme
Karin
K
Franz-Bacon
Edward P
EP
Chen
Tai Wei
TW
Ly
Yuko
Y
Kawakami
Kevin B
KB
Bacon
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D006968:Hypersensitivity, Delayed / Q000276:immunology; D017730:Ki-1 Antigen / Q000235:genetics / Q000378:metabolism; D019041:L-Selectin / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D048052:Mitogen-Activated Protein Kinase 3 / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism; D017455:Receptors, IgE / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
D017730:Ki-1 Antigen; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D019041:L-Selectin; C034832:13,14-dihydro-15-ketoprostaglandin D2; D048052:Mitogen-Activated Protein Kinase 3; D015230:Prostaglandin D2; D002118:Calcium; C036293:prostaglandin D2 receptor