Chemotactic action of prostaglandin E₂on mouse mast cells acting via the PGE₂receptor 3

Abstract

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 E 2 (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.allergy ͉ eicosanoids ͉ migration

Prostaglandin E2–EP3 Signaling Induces Inflammatory Swelling by Mast Cell Activation

“…Therefore, we propose that EP3-mediated MC activation is involved not only in the previously reported PG-related acute inflammation responses but also in Ag-independent innate immune reactions. Moreover, in addition to degranulation and cytokine release, PGE 2 has been shown to stimulate chemotaxis (or chemokinesis) and adhesion activities of MCs via the EP3 receptor (39,51,52). If this is the case, PGE 2 -EP3 signaling could function as a sensor of MCs against microenvironmental changes.…”

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…In addition, PGE 2 promotes the recruitment of CD4 + CD25 + Tregs to the tumor and has direct positive effects on tumor progression [106]. PGE 2 may also promote tissue influx of neutrophils [107], macrophages [108] and mast cells [109]. One mechanism is through PGE 2 -stimulated production of IL-8 by epithelial cells [107] and pulmonary microvascular endothelial cells [110], as well as MCP-1 by mast cells [108].…”

Prostaglandin E2 Inhibits Eosinophil Trafficking through E-Prostanoid 2 Receptors

“…At the cellular level, PGE 2 has been found to attenuate Ig-dependent degranulation of eosinophils and leukotriene biosynthesis. In contrast, PGE 2 acts as a chemoattractant for immature murine mast cells derived from bone marrow (27). Moreover, PGE 2 may favor Th2 responses over those of Th1 and promote the isotype switch to IgE (28).…”