Ww. Wang et al., COINDUCTION OF ARGINASE AND NITRIC-OXIDE SYNTHASE IN MURINE MACROPHAGES ACTIVATED BY LIPOPOLYSACCHARIDE, Biochemical and biophysical research communications, 210(3), 1995, pp. 1009-1016
In view of studies showing that not only nitric oxide synthase (NOS) a
ctivity but arginase activity is induced in rodent macrophages by lipo
polysaccharide (LPS), the objective of this study was to investigate t
he co-induction of these two enzymes and to ascertain whether common m
echanisms are involved. RAW 264.7 cells were activated by 2 mu g LPS/m
l and incubated for up to 48 hr. Inducible NOS (iNOS) and inducible ar
ginase II (AII) activities were monitored, respectively, by measuring
NO2-/NO3- accumulation in cell culture media and formation of urea (as
CO2) from L-arginine by cell lysates. AII activity increased linearly
up to at least 48 hr, whereas NO2-/NO3- formation reached a plateau w
ell before 48 hr. Immunoprecipitation experiments revealed that AII ac
counted for 90-100% of arginase activity in LPS-activated macrophages.
The inhibitor of NF-kappa B activation, pyrrolidine dithiocarbamate,
inhibited the induction of iNOS but not AII. Moreover, whereas IFN-gam
ma caused iNOS induction, AII induction was nearly abolished by IFN-ga
mma, perhaps by inhibiting transcription of the These observations ind
icate that co-induction of iNOS and AII occurs by distinct transcripti
onal mechanisms, AII induction could diminish NO production by decreas
ing L-arginine availability, and IFN-gamma can prevent AII induction.
(C) 1995 Academic Press, Inc.