Chemotactic action of prostaglandin E2 on mouse mast cells acting via the PGE2 receptor 3.
Mast cells are long-lived cells that are principally recognized for their effector function in helminth infections and allergic reactions. These cells are derived from pluripotential hematopoietic stem cells in the bone marrow that give rise to committed mast cell progenitors in the blood and are recruited to tissues, where they mature. Little is known about the chemotactic signals responsible for recruitment of progenitors and localization of mature mast cells. A mouse model was set up to identify possible mast cell progenitor chemoattractants produced during repeated allergen challenge in vivo. After the final challenge, the nasal mucosa was removed to produce conditioned medium, which was tested in chemotaxis assays against 2-wk murine bone marrow-derived c-kit+ mast cells (BMMC). A single peak of chemotactic activity was seen on reverse-phase HPLC with a retention time and electrospray mass spectrum consistent with prostaglandin E2 (PGE2). This lipid was found to be a highly potent chemoattractant for immature (2-wk) and also mature (10-wk) BMMC in vitro. Fluorescently labeled 2-wk c-kit+ BMMC, when injected intravenously, accumulated in response to intradermally injected PGE2. Analysis using TaqMan showed mRNA expression of the PGE2 receptors 3 (EP3) and 4 (EP4) on 2- and 10-wk BMMC. Chemotaxis induced by PGE2 was mimicked by EP3 agonists, blocked by an EP3 receptor antagonist, and partially inhibited by a MAPKK inhibitor. These results show an unexpected function for PGE2 in the chemotaxis of mast cells.
Weller
Charlotte L
CL
Leukocyte Biology Section, Medical Research Council and Asthma UK Centre in Allergic Mechanisms of Asthma, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
Collington
Sarah J
SJ
Hartnell
Adele
A
Conroy
Dolores M
DM
Kaise
Toshihiko
T
Barker
Jane E
JE
Wilson
Mark S
MS
Taylor
Graham W
GW
Jose
Peter J
PJ
Williams
Timothy J
TJ
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000502:physiology; D002633:Chemotaxis / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism* / Q000502:physiology*; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058308:Receptors, Prostaglandin E, EP3 Subtype
D002630:Chemotactic Factors; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D010047:Ovalbumin; D015232:Dinoprostone