Trauma increases extrahepatic arginase activity.

Abstract

BACKGROUND: Although expressed primarily in the liver, arginase activity also is present in extrahepatic tissues and specifically in macrophages, where it may play diverse physiologic roles in wound healing, cellular proliferation, and the regulation of nitric oxide production. Arginase activity in immune cells is upregulated by certain cytokines such as IL-4, IL-10, and TGF-beta and by catecholamines. Since the release of these substances is increased after trauma, we hypothesized that arginase activity would also be increased in immune cells after trauma. The current work tests this hypothesis. METHODS: A model of surgical trauma was created in C3H/HeN mice by performing an exploratory laparotomy. Tissue arginase activity and arginase I protein expression were determined. As a control, arginase activity and expression were also stimulated with the use of endotoxin. In addition, we evaluated the expression of inducible nitric oxide synthase and the accumulation of nitric oxide metabolites in plasma. RESULTS: Surgical trauma was associated with a significant increase in arginase activity in splenic and renal tissues (P < .05). Splenic macrophages from trauma animals exhibited arginase activity levels approximately 10 times those of controls (P < .05). Endotoxin alone increased arginase activity in the spleen, but this increase was less than that of trauma alone (P < .05). Arginase activity remained elevated after trauma for up to 4 days and normalized by day 7. Arginase I expression was upregulated by trauma in both splenic and renal tissue and by endotoxin in the spleen only. Despite upregulation of inducible nitric oxide synthase in trauma animals, circulating nitric oxide metabolites were decreased 2 days after trauma compared with controls (P < .05). Endotoxin-induced nitric oxide metabolites were also reduced in trauma animals compared with endotoxin treatment alone (P < .05), but this normalized by day 4. CONCLUSIONS: Extrahepatic arginase expression and activity is increased after trauma and may provide the necessary precursors for cellular proliferation and repair or may play a regulatory role in the production of nitric oxide.