Differential regulation of macrophage arginine metabolism: a
proposed role in wound healing.
Shearer, Jeffry D., John R. Richards, Charles D. Mills, Michael D.
Caldwell.
Center for Wound Healing and Reparative Medicine, Department of
Surgery, University of Minnesota, Minneapolis, MN 55455
APStracts 3:0209E, 1996.
Nitric oxide and ornithine, products of nitric oxide synthase or
arginase respectively have opposing biological activities. The effect
of mediators of leukocyte activation and inhibition on arginine
metabolism of resident mouse peritoneal exudate cells (MPEC) was
determined. Factors which increased basal nitric oxide synthase
activity, IFN-[gamma] and LPS, decreased arginase activity in intact
cells. TGF-1 decreased IFN-[gamma]-stimulated NO synthase activity
and produced a reciprocal increase in urea and ornithine release.
TGF-1 had no effect on the activity of these enzymes in LPS
-stimulated MPEC. Corticosterone(100 ng/mL) decreased the basal
activity of both enzymes. However, corticosterone inhibited NO
synthase activity and increased ornithine release in MPECs exposed to
IFN-[gamma] or LPS. The difference between arginase activity in
intact cells versus that of cell lysates suggested intracellular
inhibition of arginase activity. Products of NO synthase, NO and
citrulline, were shown to inhibit MPEC arginase activity under
maximal assay conditions. Intracellular pH was not altered by
exposure of MPEC, to LPS, IFN-[gamma], TGF- and corticosterone. This
reciprocal change in arginine metabolism is proposed to be an
important component of wound healing. Expression of NO synthase
creates a cytotoxic environment which may be important to the early
phase of wound healing. As wound healing progresses, increased
arginase activity produces an environment favorable for fibroblast
replication and collagen production.
Received 24 March 1996; accepted in final form 12 September 1996.
APS Manuscript Number E146-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996