AJP - Renal Physiology, Vol 250, Issue 4 596-F604, Copyright © 1986 by American Physiological Society
Dexamethasone and hydrogen peroxide production by mesangial cells during phagocytosis
L. Baud, J. Perez and R. Ardaillou
We have previously demonstrated that a high percentage of rat cultured
mesangial cells phagocytized serum-treated zymosan (STZ) (L. Baud, J.
Hagege, J. Sraer, E. Rondeau, J. Perez, and R. Ardaillou, J. Exp. Med. 158:
1836-1852, 1983). Phagocytosis resulted in stimulation of arachidonic acid
metabolism with generation of H2O2. Exposure of mesangial cells to
dexamethasone for 48 h produced a dose-dependent decrease in
phagocytosis-induced production of H2O2 with a 50% inhibitory concentration
of 32 nM. The decrease in H2O2 release was associated with the inhibition
of prostaglandin (PG) E2 production. The effect of dexamethasone could be
considered as due to receptor-mediated modulation of protein synthesis
since dexamethasone was not active immediately but only after a lag period
of 3 h; RU 38486, a potent competitor for dexamethasone receptors,
counteracted the reduction in H2O2 generation; and actinomycin and
cycloheximide both blunted the inhibitory effect of dexamethasone.
Pretreatment of mesangial cells with dexamethasone also produced a
dose-dependent decrease in the phagocytic capability of the cells (63%
inhibition for 1 microM dexamethasone). However, the inhibitory effect of
dexamethasone on H2O2 production expressed as percentage of control was
similar whether or not phagocytosis had been blocked by cytochalasin B.
This result and also the fact that dexamethasone inhibited H2O2 production
in cells triggered with soluble stimuli (A 23187 ionophore, PAF) suggested
that the effect of dexamethasone on H2O2 generation was independent of that
on phagocytosis. Addition of exogenous arachidonic acid reduced the effect
of dexamethasone only when its conversion into PGE2 was inhibited by
indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
