T. Nittoh et al., EFFECTS OF GLUCOCORTICOIDS ON APOPTOSIS OF INFILTRATED EOSINOPHILS AND NEUTROPHILS IN RATS, European journal of pharmacology, 354(1), 1998, pp. 73-81
The effects of glucocorticoids on the survival of rat eosinophils and
neutrophils infiltrated into the peritoneal cavity were examined. Gluc
ocorticoids including dexamethasone, prednisolone and hydrocortisone i
nhibited the survival of rat peritoneal eosinophils at 10(-6) M, where
as they prolonged survival of rat peritoneal neutrophils at 10(-8) M.
Sex steroids including estradiol and progesterone did not affect cell
survival. Dexamethasone decreased the viability of eosinophils after 3
days of incubation and maintained the viability of neutrophils until
4 days after incubation concentration dependently. The EC50 of dexamet
hasone for inhibition of the survival of eosinophils was 1.5 x 10(-8)
M, and that for the spontaneous death of neutrophils was 6.4 x 10(-10)
M, suggesting that glucocorticoids at concentrations that inhibit eos
inophil survival prolong neutrophil survival. Analysis of DNA fragment
ation of cultured eosinophils and neutrophils revealed that glucocorti
coids enhance eosinophil apoptosis but inhibit neutrophil apoptosis. T
he effects of dexamethasone on viability and DNA fragmentation were co
unteracted by the glucocorticoid receptor antagonist, mifepristone, co
ncentration dependently. These findings indicate that glucocorticoids
induce contradictory effects via the glucocorticoid receptor on rat eo
sinophils and neutrophils extravasated to an inflammatory locus such a
s the peritoneal cavity by modulating apoptosis. (C) 1998 Elsevier Sci
ence B.V. All rights reserved.