Influence of glucocorticoids on histamine release and45Calcium uptake by isolated rat mast cells

Abstract

Hydrocortisone and prednisolone inhibited the histamine release from isolated rat mast cells induced by antigen, the ionophore A23187, and compound 48/80 in the absence and in the presence of calcium. Hydrocortisone reduced the response to the different releasing agents by 50% in the concentration range 2-6 X 10(-4) M, whereas prednisolone was about 1.5 times more potent. The inhibitory effect of hydrocortisone had a rapid onset of action and maximal inhibition was observed after preincubation for 20 minutes. The effect of hydrocortisone was reversed by including 2 mM glucose in the medium. The reversal was only partial with antigen and the ionophore A23187, indicating a greater energy requirement of these releasing agents compared with compound 48/80. The inhibition of the histamine release was accompanied by a concentration-related inhibition of the 45Ca uptake, except with the ionophore. The inhibition of the 45Ca uptake was also reversed by glucose, but differences were noted concerning the influence of preincubation time. The observations are explained by an association of 45Ca to cellular material, e.g. granules, secondary to the release process. The effects of hydrocortisone and prednisolone were qualitatively identical and were not observed with estriol. The glucocorticoid inhibition of histamine release does not seem to be caused by effects on phospholipase activity or cyclic AMP metabolism. The present observations are fully consistent with an impaired mitochondrial function as the mechanism for the mast cell effects of the glucocorticoids.

Non-genomic inhibitory effect of glucocorticoids on activated peripheral blood basophils through suppression of lipid raft formation

“…Earlier studies first suggested the possibility that non‐genomic mechanisms might be involved in the rapid effect of GCs on human basophil activation through IgE‐mediated and non‐IgE‐mediated pathways. It was reported more than 25 years ago that GC inhibition of degranulation by isolated rat mast cells had a rapid onset of action and maximal inhibition was observed after preincubation of cells for only a few minutes [32]. The key finding in the current study was that GCs inhibited basophil activation, as demonstrated by expression of CD63, after cells were pretreated with GCs for 30 min.…”

Depletion of mucosal mast cell protease by corticosteroids: effect on intestinal anaphylaxis in the rat.

“…However, it is not clear whether these mechanisms are applicable to MMC, as they differ biochemically and functionally (29) from CTMC. But it is interesting to note that one action of corticosteroids may be to impair mitochondrial function (2), and it is possible that MMC have a greater energy requirement than CTMC.…”

Inhibition of Vascular Permeability Increase in Mice

“…It is well known that glucocorticoids re quire some latent period to exert their anti-inflamma tory actions [5,6], The latent period is thought to be related to the generation of the anti-inflammatory protein. Furthermore, glucocorticoids exhibit an inhi bitory effect on IgE antibody-mediated allergic reac tions through inhibiting the release of chemical medi ators from basophils and mast cells [7][8][9][10][11], Recently, it was also reported that glucocorticoids inhibit medi ator-induced increase of vascular permeability in the hamster cheek pouch [12,13]. These results suggest that glucocorticoids inhibit the increase of vascular permeability non-specifically and that this action of glucocorticoids participates in their anti-allergic ef fects.…”

“…Furthermore, time courses of the inhibi tory effect on these skin reactions were in good agree ment with those in the PCA and the mediator releaserinduced skin reactions, suggesting that the inhibition of vascular permeability increase contributes at least in part to the inhibitory effect on the PCA and the me diator releaser-induced skin reactions. On the other hand, glucocorticoids are reported to inhibit the re lease of chemical mediators from basophils and mast cells caused by IgE antibody-antigen interactions [7][8][9][10][11]. Therefore, it is considered that the inhibition of mediator release from mast cells is also participat ing in the inhibition of PCA by glucocorticoids.…”