L-arginine uptake and metabolism by lung macrophages and neutrophils following intratracheal instillation of silica in vivo.
Nitric oxide (NO) has been associated with lung inflammation following exposure to silica. L-arginine can be converted to NO and L-citrulline by nitric oxide synthase (NOS), or into urea and L-ornithine by arginase. We tested the hypothesis that after instillation of silica into rat lungs in vivo, lung inflammatory cells increase L-arginine metabolism by both NOS and arginase, which is associated with an increase in L-arginine uptake. We isolated lung inflammatory cells 3 d after silica or saline (control) exposure. The uptake of [3H]L-arginine at 24 h by cells from silica-exposed lungs (73.9 +/- 4.8%) was significantly greater than uptake by control cells (24.7 +/- 2.2%; P < 0.05) and was a saturable process. The greater [3H]L-arginine uptake by cells from silica-exposed lungs was associated with greater NO and urea production than by control cells. The uptake of [3H]L-arginine by cells from control or silica-exposed lungs was blocked in a dose-dependent manner by L-ornithine (an inhibitor of L-arginine transport) and by Nomega-nitro-L-arginine methyl ester (L-NAME) (an NOS inhibitor), but not by L-valine (an arginase inhibitor). The production of NO by cells from silica-exposed lungs was completely blocked by L-NAME. The addition of L-arginine to media resulted in dose-dependent production of NO and urea. The results show that lung inflammatory cells increase L-arginine uptake and metabolism by both NOS and arginase following in vivo silica exposure. The increase in L-arginine uptake may represent a mechanism to maintain an intracellular supply of this amino acid. NO can react to generate peroxynitrite, a potential mediator of lung injury following silica exposure.
Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, WI, USA. rschap@post.its.msw.edu
R M
RM
Schapira
J H
JH
Wiessner
J F
JF
Morrisey
U A
UA
Almagro
L D
LD
Nelin
D000818:Animals; D001120:Arginine / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D014132:Trachea; D014508:Urea / Q000378:metabolism
D009569:Nitric Oxide; D012822:Silicon Dioxide; D014508:Urea; D001120:Arginine