Arginine supplementation has been identified as advantageous in experimental wound healing. However, the mechanisms underlying this beneficial effect in tissue repair remain unresolved. Animal studies suggest that the beneficial role of arginine supplementation is mediated, at least in part through NO. The latter component mediates processes involved in tissue repair, including angiogenesis, ep...

The first arginase assays on tumor tissues led to the suggestion tha t such material in general contains a greater arginase activity than do normal tissues (e.g., 8). The postulated increase in arginine metabolism--together with the increased glycolytic reaction--was even believed to represent basic characteristics of malignant growths in general (1~). These and other controversial results (19)...

L-Arginine is the common substrate for two enzymes, arginase and nitric oxide synthase (NOS). Arginase converts L-arginine to L-ornithine, which is the precursor of polyamines, which are essential components of cell proliferation. NOS converts L-arginine to produce NO, which inhibits proliferation of many cell lines. Various human breast cancer cell lines were initially screened for the presenc...

Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with L-arginine supplementation exhibited less consistent results; however, L-citrulline, the precursor of L-arginine, may be a promising alternative. In this study, we determined the effects of L-citrulline comp...

Atherosclerotic vascular disease is the leading cause of morbidity and mortality in developed countries. While it is a complex condition resulting from numerous genetic and environmental factors, it is well recognized that oxidized low-density lipoprotein produces pro-atherogenic effects in endothelial cells (ECs) by inducing the expression of adhesion molecules, stimulating EC apoptosis, induc...

Functional integrity of the vascular endothelium is of fundamental importance for normal vascular function. A key factor regulating endothelial function is the bioavailability of nitric oxide (NO). Recently, the enzyme arginase has emerged as an important regulator of NO production by competing for l-arginine, which is a substrate for both arginase and NO synthase. Increased activity of arginas...

Myeloid suppressor cells with high arginase activity are found in tumors and spleen of mice with colon and lung cancer. These cells, described as macrophages or immature dendritic cells, deplete arginine and impair T cell proliferation and cytokine production. Although arginase activity has been described in cancer patients, it is thought to originate from tumor cells metabolizing arginine to o...

Arginase-induced L-arginine deprivation is emerging as a key mechanism for the downregulation of immune responses. We hypothesised that arginase activity increases with disease severity in HIV-seropositive patients. Our results show that peripheral blood mononuclear cells (PBMCs) from 23 HIV-seropositive patients with low CD4(+) T cell counts (≤350 cells/μl) expressed significantly more arginas...

Chronic inflammation is accompanied by impaired T-cell immunity. In the mouse, myeloid cell–associated arginase accounts for the suppression of immune reactivity in various models of tumor growth and chronic infections. Here we show that arginase I is liberated from human granulocytes, and very high activities accumulate extracellularly during purulent inflammatory reactions. Human granulocyte ...

Elevation of cAMP can overcome myelin inhibitors to encourage regeneration of the CNS. We show that a consequence of elevated cAMP is the synthesis of polyamines, resulting from an up-regulation of Arginase I, a key enzyme in their synthesis. Inhibiting polyamine synthesis blocks the cAMP effect on regeneration. Either over-expression of Arginase I or exogenous polyamines can overcome inhibitio...