Biochemical analysis of glucocorticoid-induced inhibition of IgE-mediated histamine release from mouse mast cells.
Pretreatment of mouse mast cells with 10(-7) to 10(-6) M dexamethasone (DM) during overnight sensitization with mouse IgE antibody resulted in inhibition of antigen-induced histamine release and degranulation. The inhibition of both degranulation and histamine release increased linearly with the duration of the treatment; maximal inhibition was obtained after approximately 16 hr with DM. The addition of DM to sensitized mast cells immediately before antigen challenge did not affect the antigen-induced histamine release. DM interacted directly with mast cells by binding to DM-specific cytoplasmic receptors. The treatment of mast cells with DM did not affect the binding of IgE to mast cells or intracellular cAMP levels. Bridging of cell-bound IgE anti-DNP antibody on mouse mast cells either by multivalent DNP-HSA or by anti-IgE induced phospholipid methylation at the plasma membrane and Ca++ influx into the cells. Pretreatment of mast cells with DM inhibited the antigen-induced phospholipid methylation and Ca++ uptake but failed to affect histamine release by Ca++ ionophore A23187. The results suggest that DM treatment inhibits histamine release by the inhibition of the early stage of biochemical processes leading to opening Ca++ channels but does not affect the process distal to Ca++ influx or the binding of IgE molecules to IgE receptors.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D007073:Immunoglobulin E / Q000276:immunology*; D007700:Kinetics; D008407:Mast Cells / Q000276:immunology*; D008745:Methylation; D051379:Mice; D010743:Phospholipids / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology
D005938:Glucocorticoids; D010743:Phospholipids; D011965:Receptors, Glucocorticoid; D011971:Receptors, Immunologic; D007073:Immunoglobulin E; D000001:Calcimycin; D003907:Dexamethasone; D002118:Calcium