Modulation of rat serosal mast cell biochemistry by in vivo dexamethasone administration.

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Abstract
To examine steroid-induced biochemical alterations in the mast cell secretory process, rats were injected with intramuscular dexamethasone or saline for 4 days, and serosal mast cells and lung tissue were obtained from each group. Radioligand binding studies utilizing 1-[propyl-1,2-3H]dihydroalprenolol (3H-DHA) demonstrated a 23.1 +/- 0.8% increase in rat lung beta-adrenergic receptors in steroid-treated rats, but the mast cell beta-adrenergic receptors were unaffected. Neither resting mast cell cyclic adenosine 3':5'-monophosphate (cAMP) levels nor the degree of cAMP augmentation induced by isoproterenol were changed by steroid administration. Mast cells from rats treated with dexamethasone released only 48.6 +/- 8.9 and 58.8 +/- 6.0% of the beta-hexosaminidase released from saline-treated rat mast cells when sensitized with anti-dinitrophenyl (DNP) IgE and challenged with DNP-bovine serum albumin antigen or the calcium ionophore A23187, respectively. [3H]serotonin release in cells from steroid-treated rats was 41.8 +/- 7.9 and 87.6 +/- 2.6% of control release stimulated by antigen or A23187, respectively. [14C]arachidonic acid incorporation into mast cell phospholipids followed by antigen or A23187 challenge revealed that cells from dexamethasone-treated rats release 61.3 +/- 15.6% and 62.1 +/- 11.8% of labeled metabolites, respectively, compared to controls. The addition of exogenous arachidonic acid 5 min prior to antigen challenge caused a similar decrease in mediator release in cells from saline- and steroid-treated rats (36.7 +/- 6.1 and 38.4 +/- 0.9%, respectively). When arachidonic acid was added to sensitized cells after specific antigen, no significant changes in beta-hexosaminidase release were noted in either group. Chronic in vivo dexamethasone administration markedly decreases mast cell mediator release without changing resting cAMP levels. The release of arachidonic acid metabolites is reduced in steroid-treated cells, possibly through the inhibition of phospholipases. Exogenous arachidonic acid cannot overcome this inhibition, suggesting that an earlier step in phospholipid metabolism, perhaps involving phospholipase C, may be important.