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-citrullin e by nitric oxide synthase (NOS), or into urea and L-ornithine by argi nase. We tested the hypothesis that after instillation of silica into rat lungs in vivo, lung inflammatory cells increase L-arginine metabol ism by both NOS and arginase, which is associated with an increase in L-arginine uptake. We isolated lung inflammatory cells 3 d after silic a or saline (control) exposure. The uptake of [H-3]L-arginine at 24 h by cells from silica-exposed lungs (73.9 +/- 4.8%) was significantly g reater than uptake by control cells (24.7 +/- 2.2%; P < 0.05) and was a saturable process. The greater [H-3]L-arginine uptake by cells from silica-exposed lungs was associated with greater NO and urea productio n than by control cells. The uptake of [H-3]L-arginine by cells from c ontrol or silica-exposed lungs was blocked in a dose-dependent manner by L-ornithine (an inhibitor of L-arginine transport) and by N-omega-n itro-L-arginine methyl ester (L-NAME) (an NOS inhibitor), but not by L -valine (an arginase inhibitor). The production of NO by cells from si lica-exposed lungs was completely blocked by L-NAME. The addition of L -arginine to media resulted in dose-dependent production of NO and ure a. The results show that lung inflammatory cells increase L-arginine u ptake 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 followi ng silica exposure.