Abstract
Mast cells are implicated in the pathogenesis of a broad spectrum of immunological disorders. These cells release inflammatory mediators in response to a number of stimuli, including IgE-Ag complexes. The degranulation of mast cells is modified by PGs. To begin to delineate the pathway(s) used by PGs to regulate mast cell function, we examined bone marrow-derived mast cells (BMMC) cultured from mice deficient in the EP(1), EP(2), EP(3), and EP(4) receptors for PGE(2). Although BMMCs express all four of these PGE(2) receptors, potentiation of Ag-stimulated degranulation and IL-6 cytokine production by PGE(2) is dependent on the EP(3) receptor. Consistent with the coupling of this receptor to G(alphai), PGE(2) activation of the EP(3) receptor leads to both inhibition of adenylate cyclase and increased intracellular Ca(2+). The magnitude of increase in intracellular Ca(2+) induced by EP(3) activation is similar to that observed after activation of cells with IgE and Ag. Although PGE alone is not sufficient to initiate BMMC degranulation, stimulation of cells with PGE along with PMA induces degranulation. These actions are mediated by the EP(3) receptor through signals involving Ca(2+) mobilization and/or decreased cAMP levels. Accordingly, these studies identify PGE(2)/EP(3) as a proinflammatory signaling pathway that promotes mast cell activation.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Alprostadil / analogs & derivatives*
-
Alprostadil / pharmacology
-
Animals
-
Bone Marrow Cells / drug effects
-
Bone Marrow Cells / metabolism
-
Bone Marrow Cells / physiology
-
Cell Degranulation / drug effects
-
Cell Degranulation / genetics
-
Cell Degranulation / physiology*
-
Cytokines / metabolism
-
Dinoprostone / pharmacology*
-
Interleukin-6 / biosynthesis*
-
Leukotrienes / metabolism
-
Mast Cells / drug effects
-
Mast Cells / metabolism
-
Mast Cells / physiology*
-
Mice
-
Mice, Knockout
-
Receptors, Prostaglandin E / biosynthesis
-
Receptors, Prostaglandin E / deficiency
-
Receptors, Prostaglandin E / genetics
-
Receptors, Prostaglandin E / physiology*
-
Receptors, Prostaglandin E, EP1 Subtype
-
Receptors, Prostaglandin E, EP2 Subtype
-
Receptors, Prostaglandin E, EP3 Subtype
-
Receptors, Prostaglandin E, EP4 Subtype
-
Signal Transduction / genetics
-
Signal Transduction / physiology*
-
Tetradecanoylphorbol Acetate / pharmacology
Substances
-
Cytokines
-
Interleukin-6
-
Leukotrienes
-
Ptger1 protein, mouse
-
Ptger2 protein, mouse
-
Ptger3 protein, mouse
-
Ptger4 protein, mouse
-
Receptors, Prostaglandin E
-
Receptors, Prostaglandin E, EP1 Subtype
-
Receptors, Prostaglandin E, EP2 Subtype
-
Receptors, Prostaglandin E, EP3 Subtype
-
Receptors, Prostaglandin E, EP4 Subtype
-
prostaglandin E3
-
Alprostadil
-
Dinoprostone
-
Tetradecanoylphorbol Acetate