SEPSIS INCREASES LUNG GLUTAMINE-SYNTHETASE EXPRESSION IN THE TUMOR-BEARING HOST

Acute stresses such as trauma or endotoxemia augment GLN demand and ar e associated with increased release of this amino acid from skeletal m uscle and lung as well as increased expression of glutamine synthetase (GS, the principal enzyme of GLN synthesis) in these tissues. Muscle GLN release is also increased during chronic catabolic states which ar e associated with depletion of lean body mass, such as starvation or m alignancy. We hypothesized that the expression of GS in response to an acute stress would be altered in tumor-bearing rats (TBR) experiencin g severe cachexia and therefore a previously heightened GLN demand. Ma le Fischer 344 rats were implanted with methylcholanthrene-induced fib rosarcoma tumors or underwent sham operations and pair-feeding (sham) with TBR partners. When tumor burden reached approximately 15% of carc ass weight, animals received injections of either Escherichia coli lip opolysaccharide (LPS, 1 mg/kg body wt) or saline vehicle. Rats were sa crificed 8 h after injection and lung and muscle tissue were analyzed for GS mRNA and protein via Northern and Western blot techniques, resp ectively. LPS injection caused an equivalent 4- to B-fold increase in lung and muscle GS mRNA in both TBR and sham rats (P < 0.01). LPS did not produce a significant increase in GS protein level in muscle tissu e of either group or in lung tissue of sham rats. In contrast, endotox in did lead to a 3.5-fold increase in GS protein levels in lung tissue of TBRs (P < 0.05). This increase in lung GS protein may signify the importance of the lung in maintaining GLN homeostasis during chronic c atabolic states where muscle mass is diminished. (C) 1998 Academic Pre ss.